1. bookVolume 70 (2021): Issue 1 (March 2021)
Journal Details
License
Format
Journal
eISSN
2544-4646
First Published
04 Mar 1952
Publication timeframe
4 times per year
Languages
English
access type Open Access

The Pathogenesis of Aspergillus fumigatus, Host Defense Mechanisms, and the Development of AFMP4 Antigen as a Vaccine

Published Online: 19 Mar 2021
Volume & Issue: Volume 70 (2021) - Issue 1 (March 2021)
Page range: 3 - 11
Received: 26 Aug 2020
Accepted: 11 Jan 2021
Journal Details
License
Format
Journal
eISSN
2544-4646
First Published
04 Mar 1952
Publication timeframe
4 times per year
Languages
English
Abstract

Aspergillus fumigatus is one of the ubiquitous fungi with airborne conidia, which accounts for most aspergillosis cases. In immunocompetent hosts, the inhaled conidia are rapidly eliminated. However, immunocompromised or immunodeficient hosts are particularly vulnerable to most Aspergillus infections and invasive aspergillosis (IA), with mortality from 50% to 95%. Despite the improvement of antifungal drugs over the last few decades, the therapeutic effect for IA patients is still limited and does not provide significant survival benefits. The drawbacks of antifungal drugs such as side effects, antifungal drug resistance, and the high cost of antifungal drugs highlight the importance of finding novel therapeutic and preventive approaches to fight against IA. In this article, we systemically addressed the pathogenic mechanisms, defense mechanisms against A. fumigatus, the immune response, molecular aspects of host evasion, and vaccines’ current development against aspergillosis, particularly those based on AFMP4 protein, which might be a promising antigen for the development of anti-A. fumigatus vaccines.

Keywords

Introduction

Aspergillus spp. is a genus of saprophytic fungi, which is widely distributed in nature. This genus plays an important role in environmental nitrogen and carbon recycling and relies on conidia to spread in the air (Krüger et al. 2015; Latgé and Chamilos 2019). Among the approximately 200 Aspergillus species, less than 20 are pathogenic for humans (Paulussen et al. 2017; Mead et al. 2019). Aspergillus fumigatus exerts a major influence on the number of pathogenic Aspergillus strains. Statistical data revealed that among multitudinous Aspergillus spp. isolates, A. fumigatus accounted for 50–60%, A. flavus, A. terreus, and A. niger each made up 10–15% of the isolates, and other uncommon Aspergillus spp. were less than 2% (Paulussen et al. 2017; Hoenigl et al. 2018).

Of all pathogenic Aspergillus spp., A. fumigatus with airborne conidia is a prevailing agent for human infections. The small sizes of conidia allow them to reach the lung alveoli from the natural environment effortlessly. It is estimated that humans may inhale as many as hundreds of A. fumigatus conidia every day (Alanio et al. 2017; Takazono and Izumikawa 2018). In healthy hosts, the inhaled conidia are rapidly eliminated by a competent immune system composed of innate and adaptive immunity. The innate immunity plays pivotal role in destroying most of the inhaled conidia in the respiratory tract by respiratory ciliary movement and proteins on the surface of epithelial cells, and in recognizing and engulfing the remaining conidia by alveolar phagocytes through surface pattern recognition receptors. Simultaneously, phagocytes also induce inflammatory chemokines and cytokines and recruit other immune cells to destroy surviving A. fumigatus spores and hyphae. Among them, neutrophils can prevent the formation of hyphae and kill it; monocytes can phagocytose spores to prevent fungal outbreaks. When dendritic cells phagocytose A. fumigatus, antigenic components are presented on the cell membrane surface to activate T cells and B cells, initiating adaptive immunity of the body. Whereas, if the immune responses are excessively intensive, some immunological diseases such as allergic bronchopulmonary aspergillosis will occur. In immunocompromised or immunodeficient hosts, such as the patients with immunosuppressive treatment for autoimmune disease, HIV suffers, and transplantation recipients, the growth of spores and hyphae of A. fumigatus cannot be prevented due to the decrease of neutrophils and phagocytes. Eventually, the hyphae of A. fumigatus will invade human blood vessels and spread from blood to the whole body, causing multi-system infection (Filler and Sheppard 2006). A. fumigatus is the most lethal invasive pathogenic fungus, with the mortality from invasive aspergillosis (IA) above 50%, even up to 95% (Dos Santos et al. 2020), especially for the patients with acute leukemia and hematopoietic stem cell transplantation (HSCT) (van de Peppel et al. 2018).

Despite the wide applications of antifungal drugs, they failed to provide satisfying treatment for invasive aspergillosis patients. Notably, the clear side effects of antifungal drugs such as amphotericin B’s kidney toxicity and the potential hepatotoxicity of itraconazole discouraged their clinical use. Although voriconazole had better penetration than amphotericin B and itraconazole, it might cause temporary hepatotoxicity. In addition to the side effects of antifungal drugs, drug resistance and high cost also greatly hindered the use of antifungal drugs. In response to the quest for more efficacious and safer therapeutic options, various new therapeutic drugs and new dosage forms of various therapeutic drugs are also in progress. The latest drugs, such as rifconazole and abaconazole, are being tested in various in vitro and in vivo trials (Jović et al. 2019). However, more studies still need to provide useful data on the efficacy and safety of new antifungal drugs. In consequence, the development of antifungal vaccines is highly proposed. Recently, A. fumigatus mannoprotein 4 (AFMP4) has been recognized as a virulence factor of A. fumigatus and expected to serve as an antigen for the development of anti-A. fumigatus vaccines. In this article, we systemically review the biological characters of Aspergillus spp. and the pathogenic and defense mechanisms of A. fumigatus to provide new strategies for the treatment of A. fumigatus.

Pathogenicity
Disease caused by A. fumigatus

A. fumigatus can cause a broad spectrum of aspergillosis ranging from mild to severe symptoms for immunodeficient or immunosuppressed patients, including allergic syndromes, noninvasive infections, and IA (Bonnet et al. 2017; Pagano et al. 2017; Gamaletsou et al. 2018; Xiao et al. 2020). The common diseases caused by A. fumigatus infection are as follows: (1) allergic bronchopulmonary aspergillosis (ABPA), (2) allergic sinusitis, (3) aspergilloma, (4) necrotizing pulmonary aspergillus (CNPA), (5) cutaneous aspergillosis, and (6) IA. In ABPA, the inflammation due to Aspergillus infection of the lungs primarily affects the patients with asthma, cystic fibrosis, and bronchiectasis, which cause allergy symptoms such as fever, cough, wheeze, and generalized malaise. Allergic sinusitis is a noninvasive and recurrent inflammatory sinusitis with the hypertrophic sinus and nasal polyps as the manifested symptoms in patients. Aspergilloma predominantly exhibits mycelial balls in the damaged lung bronchia, pulmonary cyst, or lung cavities, which causes a typical hemoptysis symptom in severe patients, and even threatens lives. CNPA usually occurs in patients with mild-to-moderate immunosuppression, accompanied with chronic symptoms like fever, cough, sputum, anorexia, and weight loss with a duration of 1–6 months (Barac et al. 2017). Cutaneous aspergillosis is a cutaneous manifestation of disseminated Aspergillus infection, including erythematous-to-violaceous plaques or papules, commonly characterized by an ulcer or eschar (Sato and Tamai 2019). IA is a severe infection that significantly affects immunocompromised patients, such as those who have had an organ transplant or a stem cell transplant operation. IA can affect each organ, but sinopulmonary diseases are the most common IA symptoms, including nasal congestion and pain, fever, pleuritic chest pain, and hemoptysis.

Molecular basis of A. fumigatus virulence

A. fumigatus is an opportunistic pathogen that causes ~ 90% of IA with very high mortality (Darling and Milder 2018). Why A. fumigatus dominates the human pathogenicity is confusing to clinical medical workers, which motivating scientists to explore its pathogenic mechanisms. The pathogenicity of A. fumigatus to the host was mainly manifested by a direct attack with the pathogen’s virulent factors, the hypersensitivity response of patients, or the innate and adaptive immunity of host evoked by virulent factors during the process of germinating in the host. In recent decades, especially after A. fumigatus AF293 strain genome sequencing in 2005, the virulence of A. fumigatus was shown to be multifactorial and was related to thermotolerance, cell wall composition and maintenance, resistance to immune response, toxins, nutrient uptake during invasive growth, signaling regulation, and allergens (Darling and Milder 2018; Latgé and Chamilos 2019). Besides, many molecules or genes related to the pathogenicity of A. fumigatus have been found, including galactomannan glycoprotein encoded by afmp1, hydrophobic protein Rod A, fumagillin, gliotoxin, helvolic acid, fumigaclavin C, asp-hemolysin, and so on. The genes and molecules associated with A. fumigatus virulence either were helpful for the survival of pathogens in the host, or contributed to the process of evading the immune system, such as masking the important PAMPs, inhibition of phagosome-lysosome fusion, production of antioxidants like catalase, SOD, and mannitol, or exerted multiple immunosuppressive actions on the host immunity by producing specific secondary metabolites such as gliotoxin (GT), fumagillin, actibind, and cytochalasin E.

The genes related to thermotolerance

As a thermophilic fungus, A. fumigatus can grow at 55°C and survive at temperatures above 75°C. This ability facilitates to thrive in dead or decayed organic matters and to infect mammalian host cells. Thus, the genes related to thermotolerance contribute to the virulence of A. fumigatus. Five genes have been proved to be associated with the thermotolerance of A. fumigatus (thtA, cgrA, afpmt1, kre2/afmnt1, and hsp1/asp f 12). The thtA gene is necessary for the growth of A. fumigatus at 48°C, but it is not involved in the pathogenicity of A. fumigatus. The afpmt1 gene encodes for one mannosyl transferase, which is essential for the growth of A. fumigatus over 37°C. It was found that the Δafmnt1 mutant was attenuated in a mouse infection model and more sensitive to azoles (Wagener et al. 2008).

Toxins

A. fumigatus produce toxins for protection against predators and competitors, and they can directly attack the host and contribute to the pathogenesis of the fungus. Many toxins are secondary metabolites of fungi. They can affect the synthesis of DNA, RNA, and proteins, or alter cell membrane and impair cellular functions. Many toxins and relevant genes of A. fumigatus have been studied, such as diffusible toxic substances from conidia, gliotoxin (gliP and gliZ), mitogillin (res/mitF/aspf1), hemolysin (aspHS), verruculogen, fumagillin, and the transcription factor laeA. Gliotoxin is the most potent toxin produced by A. fumigatus (Zhang et al. 2019), which can suppress macrophage phagocytosis, T cell proliferation, cytotoxic T cell response, and monocyte apoptosis (Schlam et al. 2016; Schmidt et al. 2017; Fraga-Silva et al. 2019). Gliotoxin can also inhibit the NADPH of neutrophils (Tsunawaki et al. 2004), suppress ROS production, and impair the neutrophil’s phagocytic capacity (Orciuolo et al. 2007). In addition, it should be noted that the transcription factor laeA is a crucial regulator for secondary metabolite biosynthesis (Pfannenstiel et al. 2017), and it has been proved that laeA deletion in A. fumigatus inhibited the production of almost all secondary metabolites containing gliotoxin (Arias et al. 2018).

Allergens

Moreover, A. fumigatus can produce a large number of allergens; among them 23 have their official names ranging from Asp f1 to Asp f34 (available at: http://www.allergen.org/, updated on July 11, 2019). Some allergens show toxic or enzymatic activities, which are related to the virulence. Other allergenic molecules have no virulence functions. All Aspergillus allergens are likely to trigger a Type I hypersensitivity response in patients and induce a high-affinity IgE antibody production. Aspergillus allergens can cause hypersensitivities in immunocompetent patients, such as ABPA, allergic rhinosinusitis, asthma, and aspergilloma. In immunocompromised patients, these allergenic molecules can significantly increase the risk of aspergillosis. Many Aspergillus allergens have been explored and developed for diagnostic purposes (Masaki et al. 2017).

Other pathogenic factors

So far, none of the pathogenic factors is unique to A. fumigatus, and it is necessary to further investigate why A. fumigatus is more pathogenic than other common conditional pathogens. Some scholars believed that, unlike other human pathogenic bacteria such as Candida and Cryptococcus, the pathogenicity of A. fumigatus is not caused by one or several pathogenic factors but caused by the result of its unique biological characteristics such as growth and metabolism and the joint action of multiple pathogenic factors.

Recently, based on the homology between fungal endoether glucokinase and AnmK kinase of bacterial cell wall circulatory metabolism, we proposed the hypothesis that fungal cell wall has a mechanism similar to that of bacterial cell wall circulatory metabolism, which plays a role in the growth and reproduction of fungi. Whether this hypothesis is correct and related to the pathogenicity of A. fumigatus needs to be further confirmed by research.

Defense mechanism against A. Fumigatus
Host immunity to A. fumigatus
Innate defense immunity

Anatomical barriers. At the entry point of airborne conidia, the upper respiratory tract’s airway epithelium is the first defensive line of innate host immunity against A. fumigatus. As an airway epithelium cell, the mucous secreting cell can secrete mucus to trap inhaled conidia. Another airway epithelium cell, a ciliated cell, can drive the trapped conidia to the oropharyngeal junction (van de Veerdonk et al. 2017). In this way, a significant number of A. fumigatus are expulsed from the lung. The respiratory epithelium can also secrete some peptides or enzymes to combat A. fumigatus, indicating that chitinase produced by epithelium can damage chitin on the cell wall of A. fumigatus (Garth et al. 2018).

Professional phagocytes and classical signaling pathways. The dominant role of phagocytes defense against A. fumigatus in vivo and in vitro has been reported (Liu et al. 2017; Almeida et al. 2019; Mackel and Steele 2019). The primary phagocytes responsible for the phagocytosis of A. fumigatus are alveolar macrophages (AM) and neutrophils.

In the lung of the immunocompetent host, certain soluble recognition receptors produced by alveolar macrophages such as Pentraxin 3 (PTX3) and surface protein-D (SP-D) can immediately bind to the inhaled conidia of A. fumigatus, and enhance the phagocytosis of alveolar macrophages (Smole et al. 2020). Alveolar macrophages then recognize and swallow the conidia through the TLR2/4 and Dectin-1. Toll-like receptors (TLRs) are type I membrane receptors that function in recognition of PAMPs and an intracellular TLR domain required for downstream signaling. TLRs can recognize pathogens and activate transcription factors such as NF-κB, which mediate the expression of inflammatory cytokines and chemokines (Anthoney et al. 2018). Some studies implicated the membrane receptors TLR2 and TLR4 were the crucial recognition components for host defense against A. fumigatus (Dai et al. 2019). An essential role for TLR2 and TLR4 in cytokine production against A. fumigatus has been established in many in vitro studies (Briard et al. 2019; Gupta et al. 2019). Dectin-1 is a type II transmembrane protein, which is highly expressed in macrophages, neutrophils, and DCs. Dectin-1 can recognize β-glucan on germinating conidian but cannot identify the resting conidia, allowing macrophages to differentiate the various forms of A. fumigatus (Li et al. 2019; Dutta et al. 2020). Alveolar macrophages capture conidia leading to a proinflammatory response accompanied by the secretion of many cytokines and chemokines, including TNF-α and CXCL2 (Chemokine (C-X-C motif) ligand 2), which are essential activators for neutrophil recruitment (Guo et al. 2020). The conidia escaped from the phagocytosis by alveolar macrophages continue to germinate and spread. Proinflammatory factors derived by alveolar macrophages and epithelial cells recruit neutrophils to the infection site. Neutrophils perform an effective elimination of the germinating conidia and hyphae.

In the immunocompetent lung, conidia are immediately trapped by the soluble recognition receptors (PTX3, SP-D), promoting conidial phagocytosis by alveolar macrophage (AM). AM also captures conidia through TLRs and Dectin-1, leading to a proinflammatory response. The escaped conidia continue to germinate and penetrate through the alveolar epithelial cells. Neutrophils employ the processes of NET formation, degranulation, and lactoferrin production to inactivate germinating conidia and hyphae. Dendritic cells phagocytose, and process germinated conidia for antigens presentation to T cells, and finally activate an adaptive immune response to A. fumigatus (Garth and Steele 2017).

Mechanism of innate immune cells removing A. fumigatus. The mechanism includes phagocytosis, reactive oxygen species (ROS) generations mediated by nicotinamide adenine dinucleotide phosphate-oxidase (NADPH), lactoferrin production, and neutrophil extracellular traps (NETs) formation (Schoen et al. 2019; Souza et al. 2019; Shopova et al. 2020). ROS production responds to swollen conidia, but not resting conidia, through NADPH oxidase activation (Ferling et al. 2020; Khani et al. 2020). It has been demonstrated that the ROS-producing complex plays a crucial fungicidal role during A. fumigatus infection (Shen et al. 2016). NETs are networks of extracellular fibers, mainly composed of DNA from neutrophils. The NET formation is induced by a variety of proinflammatory mediators such as IL-8. It is significant for defense against large pathogens, such as hyphae of A. fumigatus (Li et al. 2020). It has been demonstrated both in vitro and in vivo, NET formation is dependent on NADPH oxidase and ROS generation (Khan et al. 2019; Ravindran et al. 2019). In addition, dendritic cells (DCs) play a well-established role in the host defense against A. fumigatus. Immature DCs can phagocytose conidia and hyphae through PRRs and present the processed antigens of A. fumigatus to host T cells, leading to the activation of adaptive immune responses (Wang et al. 2017).

Adaptive immunity mechanism

The elimination of the daily-inhaled conidia mainly depends on the innate immune response, but the treatment for serious Aspergillus infections relies on the cooperation of the adaptive immune system, which responds to the signaling generated by innate immunity. Lymphocytes T and B represent the two main parts of the adaptive defensive system.

Role of T cells in adaptive immunity. The T cell immunity system interacts with the innate immune response in many ways. For instance, DCs recruit at the infection sites can load and migrate the A. fumigatus antigen to lymph nodes, leading to T lymphocytes’ activation (Wang et al. 2017). CD4+ T cells are the dominating organizer, which play a major role in antifungal immunity. These activated T cells are able to invoke phagocytes or restrict the immune response. The initiating of CD4+ T cell immunity occurred between TCR and its cognate antigens on the DC cells. The excessive inflammatory response secreted by the activated T cells can induce the naïve T cells to differentiate into CD4 T help (Th) subsets while damaging the incident tissues and contributing to the invasive infections of A. fumigatus. Th1 response was the predominant cell type that involved the protective immune response to the host through the production of pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and TNF-α. In contrast, Th2 immune response was associated with the germination of fungal and exacerbation of disease as well as induced the alternatively activated macrophages in the defense against A. fumigatus. The balance between Th1 and Th2 subset determined the quality and outcome of host immune responses. It was also found that Th17 played multiple roles in clearing infections by participating in the production of proinflammatory genes and antimicrobial peptides, recruitment, and activation of neutrophils (Pathakumari et al. 2020). T cell immunity against fungal infections primes Th1 type response (Shenoy et al. 2017). However, in patients with aspergillosis, the predominance of Th2 T cells’ immune response was conducted to exacerbate disease (Dewi et al. 2017). Besides, DCs contribute to a damaging inflammatory response by stimulating the Th17 cells and producing IL-23 (Movahed et al. 2018).

Humoral immunity to A. fumigatus. The function of Aspergillus-specific antibodies in immunocompromised patients with IA has been investigated (Boniche et al. 2020). Early researches indicated that the antibody responses failed to provide effective protection against IA or played only a minor role in fighting aspergillosis (Cutler et al. 2007). However, recent research reported that β-1,3-glucan specific antibodies could not only inhibit Aspergillus hyphae but also protect CD2F1 mice against Aspergillus challenge (Matveev et al. 2019). Although it is generally acknowledged that T cells immunity plays a vital role in combating fungal aspergillosis (Diaz-Arevalo and Kalkum 2017), there are a variety of ways, such as opsonization, complement activation, and virulence factors neutralization, in which antibodies affect T cells response and suppress the growth, adherence, and germination of fungi (Liedke et al. 2017; Ulrich and Ebel 2020).

Progress of anti-A. fumigatus vaccines development

Despite the wide applications of antifungal drugs, they failed to provide satisfying treatment for IA patients. The therapy with antifungal drugs is often associated with side effects, drug-resistance, and high costs. To overcome these disadvantages, the development of alternative methods, including antifungal vaccines, is highly desirable. Antifungal vaccine studies’ primary tool is the employment of fungal particulate forms, homogenates, or recombinant proteins. Some studies revealed that the immunization with conidia, mycelia extracts, or fungal culture filtrates induced effective protection against Aspergillus infections (Muthu et al. 2018; Pérez-Cantero et al. 2019). The heat-killed mutant strain was also reported to be a broad-spectrum fungal vaccine that induced host protection against common invasive fungal infections in both immunocompetent and immunocompromised hosts (Wang et al. 2019). However, the crude extracts commonly consist of abundant fungal components as various carbohydrates, nucleic acids, or even some toxins (Shishodia et al. 2019). Thus, vaccination using purified recombinant antigenic protein or peptide-based vaccine (Da Silva et al. 2020) is a more popular method in antifungal vaccine studies, whereas the possibility of potential severe anaphylaxis remains.

Obstacles in vaccine development

Although recently there is some progress published on the study of vaccines against A. fumigatus (Chauvin et al. 2019; Khani et al. 2020), several significant obstacles remain to be overcome for producing effective vaccine (Levitz 2017). First of all, since A. fumigatus is an opportunistic pathogen and most invasive infections appear in the immunocompromised population, the induction of an effective adaptive immunity in such individuals is a real challenge. One of the feasible measures is the prophylactic vaccination, especially in target population, such as the patients waiting for bone marrow transplant and the patients before the treatment with immunosuppressive agents. Another major problem in developing a vaccine against A. fumigatus is related to the fungus’ molecular complexity. The extract of A. fumigatus is a mixture containing up to 200 different proteins, glycoproteins, and compounds of low molecular weights. In addition, safety issues should also be well addressed because a wide range of allergic diseases correlates with Aspergillus allergens. The potential of activating an adverse immunoreaction is also an intractable problem (Dewi et al. 2017).

Adaptive immunity induced by anti-A. fumigatus vaccines

Currently, some A. fumigatus allergens were identified based on their reactivity to patients’ antibodies. Some of these allergens are not effective antigens for vaccine development because they primarily induce Th2 cell response but cannot provide adequate protection against Aspergillus infection. Nevertheless, a recombinant allergen of A. fumigatus – Aspf3 was confirmed to induce protective response when presented mixed with TM adjuvant in a murine inhalation model (Namvar et al. 2015). It was also reported that various yeast genera could activate innate CD8+ T lymphocyte response and generate broad antifungal protection (Bazan et al. 2018). It suggested yeasts as a potential antifungal vaccine candidate to activate antigen-specific CD8+ T cell responses effectively.

For a long time, most antifungal vaccine research intended to activate memory T lymphocytes and raise a Th1 type immune response that would produce some favorable cytokines to enhance phagocytosis or T cell killing (Upadhya et al. 2016). Most studies suggested that the protective antifungal reactions induced by vaccines are cell-mediated immune responses. However, some recent investigations focused on protective antibodies. One β-glucan conjugate vaccine was shown to provide good protection against Candida albicans and A. fumigatus (Catellani et al. 2020). The serum of vaccinated mice significantly inhibited the growth of fungus hyphae. The mechanism of the β-glucan conjugate vaccine might involve specific anti-β-glucan antibody (Matveev et al. 2019).

Optimizing vaccination schedules with A. fumigatus mannoprotein (AFMP)

The cell wall of fungi is primarily defensive to a hostile environment (Ruiz-Herrera and Ortiz-Castellanos 2019). Except for physical protection, one central role of the fungus cell wall is the interaction with the hosts. Therefore, the cell wall components are usually the targets to be attacked by the immune cells in hosts. The cell wall of A. fumigatus is mainly composed of polysaccharides and proteins. The polysaccharides consist of glucan, mannose, and chitin, which constitute a three-dimensional network. β-(1,3)-glucan branched with β-(1,6)-glucan forms the wall’s skeleton. Chitin, a polymer of N-acetylglucosamine is covalently linked to β-glucan. Several proteins of the cell wall are mannosylated. The role of some mannoprotein has been investigated and suggested as antigenic determinants for serodiagnosis.

Mannoproteins (MPs) are natural glycoconjugates expressed mainly on the fungal surface and released into the culture medium during fungal growth. MPs have been implicated as important antigens involved in the induction of T cell-mediated immunity (Schülke 2018; Paulovičová et al. 2019). Therefore, MP may have potential use as an immunomodulator in patients at high risk of IA.

The afmp genes were reported to encode some cell wall MPs of A. fumigatus. Among them, afmp1 encodes a protein-AFMP1 with 284 amino acids, which contains some similar sequences present in MP of Penicillium marneffei (Muszewska et al. 2017). AFMP2 also includes a few domains of MP1 (Woo et al. 2018). Remarkably, specific AFMP1 and AFMP2 antibodies were found in the aspergillosis or aspergilloma patients during A. fumigatus infections (Woo et al. 2018). Moreover, recombinant AFMP1 protein was also applied in the ELISA assay to detect specific AFMP1 antibodies in hosts, which greatly contributes to the rapid diagnosis of A. fumigatus-related aspergillosis (Woo et al. 2018). Based on this research, another two A. fumigatus MPs, AFMP3, and AFMP4 proteins were discovered during BLASTP searching conserved sequence domains of AFMP2 (Woo et al. 2018). Furthermore, it was demonstrated that AFMP1 and AFMP4 monoclonal antibodies had been generated and used to develop two ELISA methods to detect AFMP1 and AFMP4. These antigen-capture ELISA methods can rapidly and specifically detect AFMP1 or AFMP4 in the cultures of A. fumigatus without the cross-reactivity with other pathogenic Aspergillus species (Woo et al. 2018).

In MP1 and AFMP1~AFMP4 proteins, there is a putative signal peptide at the N-terminal site, which instructs secretory proteins to the endoplasmic reticulum route (Woo et al. 2018), as well as several homologous conserved domains detected through phylogenetic analysis. Considering that the virulence role of Penicillium marneffei mannoprotein 1 (MP1) has been confirmed (Woo et al. 2018), AFMPs may contribute to the virulence of A. fumigatus likewise. Our collaborators compared the difference in virulence between wild A. fumigatus and various afmp mutants (Woo et al. 2018). The results showed that among the four afmp1-afmp4 single knockdown mutants, the virulence of A. fumigatus distinctly decreased only in the afmp4 mutant. The mice infected by the conidia of afmp1-afmp3 single knockdown strains did not distinguish the survival rates in the mice challenged with conidia of wild type A. fumigatus. It implied that afmp1, afmp2, afmp3 might not be the crucial toxic factors, whereas afmp4 is very likely to be a decisive virulence factor for A. fumigatus and may be used as a promising antigen for the development of vaccines against A. fumigatus.

Conclusions

The multifactorial virulence factors and complex pathogenic mechanism of A. fumigatus put forward higher requirements for the prevention and control of fungal. Advances in the understanding of pathogenicity and host immune response to A. fumigatus would be conductive to propose new strategies for antifungal vaccines. The AFMP4 protein of A. fumigatus, which has been identified at the molecular levels, might serve as a promising candidate antigen for developing vaccines against invasive aspergillosis. Alternatively, a pan-fungal vaccine with a broader antifungal spectrum derived from the conserved fungal cell surface epitopes might be the most promising antifungal vaccine in the future. Also, several studies of animal models, adjuvants, and immunomodulators would provide novel strategies for the design of antifungal vaccines. Nevertheless, with antifungal vaccines’ progress, these vaccines’ efficacy and efficiency need to be improved.

Alanio A, Desnos-Ollivier M, Garcia-Hermoso D, Bretagne S. Investigating clinical issues by genotyping of medically important fungi: why and how? Clin Microbiol Rev. 2017 Jul;30(3):671–707. https://doi.org/10.1128/CMR.00043-16AlanioADesnos-OllivierMGarcia-HermosoDBretagneS. Investigating clinical issues by genotyping of medically important fungi: why and how?Clin Microbiol Rev.2017Jul;30(3):671707. https://doi.org/10.1128/CMR.00043-1610.1128/CMR.00043-16547522428490578Search in Google Scholar

Almeida MC, Antunes D, Silva BMA, Rodrigues L, Mota M, Borges O, Fernandes C, Gonçalves T. Early interaction of alternaria infectoria conidia with macrophages. Mycopathologia. 2019 Jun;184(3):383–392. https://doi.org/10.1007/s11046-019-00339-6AlmeidaMCAntunesDSilvaBMARodriguesLMotaMBorgesOFernandesCGonçalvesT. Early interaction of alternaria infectoria conidia with macrophages. Mycopathologia.2019Jun;184(3):383392. https://doi.org/10.1007/s11046-019-00339-610.1007/s11046-019-00339-631183740Search in Google Scholar

Anthoney N, Foldi I, Hidalgo A. Toll and Toll-like receptor signalling in development. Development. 2018 May 01;145(9):dev156018. https://doi.org/10.1242/dev.156018AnthoneyNFoldiIHidalgoA. Toll and Toll-like receptor signalling in development. Development.2018May 01;145(9):dev156018. https://doi.org/10.1242/dev.15601810.1242/dev.15601829695493Search in Google Scholar

Arias M, Santiago L, Vidal-García M, Redrado S, Lanuza P, Comas L, Domingo MP, Rezusta A, Gálvez EM. Preparations for invasion: modulation of host lung immunity during pulmonary aspergillosis by gliotoxin and other fungal secondary metabolites. Front Immunol. 2018 Nov 6;9:2549. https://doi.org/10.3389/fimmu.2018.02549AriasMSantiagoLVidal-GarcíaMRedradoSLanuzaPComasLDomingoMPRezustaAGálvezEM. Preparations for invasion: modulation of host lung immunity during pulmonary aspergillosis by gliotoxin and other fungal secondary metabolites. Front Immunol.2018Nov 6;9:2549. https://doi.org/10.3389/fimmu.2018.0254910.3389/fimmu.2018.02549623261230459771Search in Google Scholar

Barac A, Vukicevic TA, Ilic AD, Rubino S, Zugic V, Stevanovic G. Complications of chronic necrotizing pulmonary aspergillosis: review of published case reports. Rev Inst Med Trop São Paulo. 2017; 59(0):e19. https://doi.org/10.1590/s1678-9946201759019BaracAVukicevicTAIlicADRubinoSZugicVStevanovicG. Complications of chronic necrotizing pulmonary aspergillosis: review of published case reports. Rev Inst Med Trop São Paulo.2017; 59(0):e19. https://doi.org/10.1590/s1678-994620175901910.1590/s1678-9946201759019Search in Google Scholar

Bazan SB, Walch-Rückheim B, Schmitt MJ, Breinig F. Maturation and cytokine pattern of human dendritic cells in response to different yeasts. Med Microbiol Immunol (Berl). 2018 Feb;207(1):75–81. https://doi.org/10.1007/s00430-017-0528-8BazanSBWalch-RückheimBSchmittMJBreinigF. Maturation and cytokine pattern of human dendritic cells in response to different yeasts. Med Microbiol Immunol (Berl).2018Feb;207(1):7581. https://doi.org/10.1007/s00430-017-0528-810.1007/s00430-017-0528-829164392Search in Google Scholar

Boniche C, Rossi SA, Kischkel B, Barbalho FV, Moura ÁND, Nosanchuk JD, Travassos LR, Taborda CP. Immunotherapy against systemic fungal infections based on monoclonal antibodies. J Fungi (Basel). 2020 Feb 29;6(1):31. https://doi.org/10.3390/jof6010031BonicheCRossiSAKischkelBBarbalhoFVMouraÁNDNosanchukJDTravassosLRTabordaCP. Immunotherapy against systemic fungal infections based on monoclonal antibodies. J Fungi (Basel).2020Feb 29;6(1):31. https://doi.org/10.3390/jof601003110.3390/jof6010031715120932121415Search in Google Scholar

Bonnet S, Duléry R, Regany K, Bouketouche M, Magro L, Coiteux V, Alfandari S, Berthon C, Quesnel B, Yakoub-Agha I. Long-term follow up of invasive aspergillosis in allogeneic stem cell transplantation recipients and leukemia patients: differences in risk factors and outcomes. Curr Res Transl Med. 2017 Apr-Jun;65(2):77–81. https://doi.org/10.1016/j.retram.2017.05.003BonnetSDuléryRReganyKBouketoucheMMagroLCoiteuxVAlfandariSBerthonCQuesnelBYakoub-AghaI. Long-term follow up of invasive aspergillosis in allogeneic stem cell transplantation recipients and leukemia patients: differences in risk factors and outcomes. Curr Res Transl Med.2017Apr-Jun;65(2):7781. https://doi.org/10.1016/j.retram.2017.05.00310.1016/j.retram.2017.05.00328689016Search in Google Scholar

Briard B, Karki R, Malireddi RKS, Bhattacharya A, Place DE, Mavuluri J, Peters JL, Vogel P, Yamamoto M, Kanneganti TD. Fungal ligands released by innate immune effectors promote inflammasome activation during Aspergillus fumigatus infection. Nat Microbiol. 2019 Feb;4(2):316–327. https://doi.org/10.1038/s41564-018-0298-0BriardBKarkiRMalireddiRKSBhattacharyaAPlaceDEMavuluriJPetersJLVogelPYamamotoMKannegantiTD. Fungal ligands released by innate immune effectors promote inflammasome activation during Aspergillus fumigatus infection. Nat Microbiol.2019Feb;4(2):316327. https://doi.org/10.1038/s41564-018-0298-010.1038/s41564-018-0298-0661950130510167Search in Google Scholar

Catellani M, Lico C, Cerasi M, Massa S, Bromuro C, Torosantucci A, Benvenuto E, Capodicasa C. Optimised production of an anti-fungal antibody in Solanaceae hairy roots to develop new formulations against Candida albicans. BMC Biotechnol. 2020 Dec;20(1):15. https://doi.org/10.1186/s12896-020-00607-0CatellaniMLicoCCerasiMMassaSBromuroCTorosantucciABenvenutoECapodicasaC. Optimised production of an anti-fungal antibody in Solanaceae hairy roots to develop new formulations against Candida albicans. BMC Biotechnol.2020Dec;20(1):15. https://doi.org/10.1186/s12896-020-00607-010.1186/s12896-020-00607-0706903332164664Search in Google Scholar

Chauvin D, Hust M, Schütte M, Chesnay A, Parent C, Moreira GMSG, Arroyo J, Sanz AB, Pugnière M, Martineau P, et al. Targeting Aspergillus fumigatus Crf transglycosylases with neutralizing antibody is relevant but not sufficient to erase fungal burden in a neutropenic rat model. Front Microbiol. 2019 Mar 26;10:600. https://doi.org/10.3389/fmicb.2019.00600ChauvinDHustMSchütteMChesnayAParentCMoreiraGMSGArroyoJSanzABPugnièreMMartineauP. Targeting Aspergillus fumigatus Crf transglycosylases with neutralizing antibody is relevant but not sufficient to erase fungal burden in a neutropenic rat model. Front Microbiol.2019Mar 26;10:600. https://doi.org/10.3389/fmicb.2019.0060010.3389/fmicb.2019.00600644362730972049Search in Google Scholar

Cutler JE, Deepe GS Jr, Klein BS. Advances in combating fungal diseases: vaccines on the threshold. Nat Rev Microbiol. 2007 Jan;5(1):13–28. https://doi.org/10.1038/nrmicro1537CutlerJEDeepeGSJrKleinBS. Advances in combating fungal diseases: vaccines on the threshold. Nat Rev Microbiol.2007Jan;5(1):1328. https://doi.org/10.1038/nrmicro153710.1038/nrmicro1537221430317160002Search in Google Scholar

Da Silva LBR, Taborda CP, Nosanchuk JD. Advances in fungal peptide vaccines. J Fungi (Basel). 2020 Jul 25;6(3):119. https://doi.org/10.3390/jof6030119Da SilvaLBRTabordaCPNosanchukJD. Advances in fungal peptide vaccines. J Fungi (Basel).2020Jul 25;6(3):119. https://doi.org/10.3390/jof603011910.3390/jof6030119755841232722452Search in Google Scholar

Dai C, Wu J, Chen C, Wu X. Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection. Exp Eye Res. 2019 May;182:19–29. https://doi.org/10.1016/j.exer.2019.02.020DaiCWuJChenCWuX. Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection. Exp Eye Res.2019May;182:1929. https://doi.org/10.1016/j.exer.2019.02.02010.1016/j.exer.2019.02.02030853520Search in Google Scholar

Darling BA, Milder EA. Invasive aspergillosis. Pediatr Rev. 2018 Sep;39(9):476–478. https://doi.org/10.1542/pir.2017-0129DarlingBAMilderEA. Invasive aspergillosis. Pediatr Rev.2018Sep;39(9):476478. https://doi.org/10.1542/pir.2017-012910.1542/pir.2017-012930171061Search in Google Scholar

Dewi I, van de Veerdonk F, Gresnigt M. The multifaceted role of T-helper responses in host defense against Aspergillus fumigatus. J Fungi (Basel). 2017 Oct 04;3(4):55. https://doi.org/10.3390/jof3040055DewiIvan de VeerdonkFGresnigtM. The multifaceted role of T-helper responses in host defense against Aspergillus fumigatus. J Fungi (Basel).2017Oct 04;3(4):55. https://doi.org/10.3390/jof304005510.3390/jof3040055575315729371571Search in Google Scholar

Diaz-Arevalo D, Kalkum M. CD4+ T cells mediate aspergillosis vaccine protection. Methods Mol Biol. 2017;1625:281–293. https://doi.org/10.1007/978-1-4939-7104-6_19Diaz-ArevaloDKalkumM. CD4+ T cells mediate aspergillosis vaccine protection. Methods Mol Biol.2017;1625:281293. https://doi.org/10.1007/978-1-4939-7104-6_1910.1007/978-1-4939-7104-6_1928584997Search in Google Scholar

Dos Santos RAC, Steenwyk JL, Rivero-Menendez O, Mead ME, Silva LP, Bastos RW, Alastruey-Izquierdo A, Goldman GH, Rokas A. Genomic and phenotypic heterogeneity of clinical isolates of the human pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis. Front Genet. 2020 May 12;11:459. https://doi.org/10.3389/fgene.2020.00459Dos SantosRACSteenwykJLRivero-MenendezOMeadMESilvaLPBastosRWAlastruey-IzquierdoAGoldmanGHRokasA. Genomic and phenotypic heterogeneity of clinical isolates of the human pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis. Front Genet.2020May 12;11:459. https://doi.org/10.3389/fgene.2020.0045910.3389/fgene.2020.00459723630732477406Search in Google Scholar

Dutta O, Espinosa V, Wang K, Avina S, Rivera A. Dectin-1 promotes type I and III interferon expression to support optimal antifungal immunity in the lung. Front Cell Infect Microbiol. 2020 Jul 8;10:321. https://doi.org/10.3389/fcimb.2020.00321DuttaOEspinosaVWangKAvinaSRiveraA. Dectin-1 promotes type I and III interferon expression to support optimal antifungal immunity in the lung. Front Cell Infect Microbiol.2020Jul 8;10:321. https://doi.org/10.3389/fcimb.2020.0032110.3389/fcimb.2020.00321736081132733815Search in Google Scholar

Ferling I, Dunn JD, Ferling A, Soldati T, Hillmann F. Conidial melanin of the human-pathogenic fungus Aspergillus fumigatus disrupts cell autonomous defenses in amoebae. MBio. 2020 May 26; 11(3):e00862–20. https://doi.org/10.1128/mBio.00862-20FerlingIDunnJDFerlingASoldatiTHillmannF. Conidial melanin of the human-pathogenic fungus Aspergillus fumigatus disrupts cell autonomous defenses in amoebae. MBio.2020May 26; 11(3):e0086220. https://doi.org/10.1128/mBio.00862-2010.1128/mBio.00862-20725120832457245Search in Google Scholar

Filler SG, Sheppard DC. Fungal invasion of normally non-phagocytic host cells. PLoS Pathog. 2006;2(12):e129. https://doi.org/10.1371/journal.ppat.0020129FillerSGSheppardDC. Fungal invasion of normally non-phagocytic host cells. PLoS Pathog.2006;2(12):e129. https://doi.org/10.1371/journal.ppat.002012910.1371/journal.ppat.0020129175719917196036Search in Google Scholar

Fraga-Silva TFC, Mimura LAN, Leite LCT, Borim PA, Ishikawa LLW, Venturini J, Arruda MSP, Sartori A. Gliotoxin aggravates experimental autoimmune encephalomyelitis by triggering neuroinflammation. Toxins (Basel). 2019 Jul 26;11(8):443. https://doi.org/10.3390/toxins11080443Fraga-SilvaTFCMimuraLANLeiteLCTBorimPAIshikawaLLWVenturiniJArrudaMSPSartoriA. Gliotoxin aggravates experimental autoimmune encephalomyelitis by triggering neuroinflammation. Toxins (Basel).2019Jul 26;11(8):443. https://doi.org/10.3390/toxins1108044310.3390/toxins11080443672273331357414Search in Google Scholar

Gamaletsou MN, Walsh TJ, Sipsas NV. Invasive fungal infections in patients with hematological malignancies: emergence of resistant pathogens and new antifungal therapies. Turk J Haematol. 2018 Feb 26;35(1):1–11. https://doi.org/10.4274/tjh.2018.0007GamaletsouMNWalshTJSipsasNV. Invasive fungal infections in patients with hematological malignancies: emergence of resistant pathogens and new antifungal therapies. Turk J Haematol.2018Feb 26;35(1):111. https://doi.org/10.4274/tjh.2018.000710.4274/tjh.2018.0007584376829391334Search in Google Scholar

Garth JM, Mackel JJ, Reeder KM, Blackburn JP, Dunaway CW, Yu Z, Matalon S, Fitz L, Steele C. Acidic mammalian chitinase negatively affects immune responses during acute and chronic Aspergillus fumigatus exposure. Infect Immun. 2018 Apr 30;86(7):e00944–17. https://doi.org/10.1128/IAI.00944-17GarthJMMackelJJReederKMBlackburnJPDunawayCWYuZMatalonSFitzLSteeleC. Acidic mammalian chitinase negatively affects immune responses during acute and chronic Aspergillus fumigatus exposure. Infect Immun.2018Apr 30;86(7):e0094417. https://doi.org/10.1128/IAI.00944-1710.1128/IAI.00944-17601365729712728Search in Google Scholar

Garth JM, Steele C. Innate lung defense during invasive aspergillosis: new mechanisms. J Innate Immun. 2017;9(3):271–280. https://doi.org/10.1159/000455125GarthJMSteeleC. Innate lung defense during invasive aspergillosis: new mechanisms. J Innate Immun.2017;9(3):271280. https://doi.org/10.1159/00045512510.1159/000455125547523028231567Search in Google Scholar

Guo Y, Kasahara S, Jhingran A, Tosini NL, Zhai B, Aufiero MA, Mills KAM, Gjonbalaj M, Espinosa V, Rivera A, et al. During Aspergillus infection, monocyte-derived DCs, neutrophils, and plasmacytoid DCs enhance innate immune defense through CXCR3-dependent crosstalk. Cell Host Microbe. 2020 Jul 8;28(1):104–116.e4. https://doi.org/10.1016/j.chom.2020.05.002GuoYKasaharaSJhingranATosiniNLZhaiBAufieroMAMillsKAMGjonbalajMEspinosaVRiveraA. During Aspergillus infection, monocyte-derived DCs, neutrophils, and plasmacytoid DCs enhance innate immune defense through CXCR3-dependent crosstalk. Cell Host Microbe.2020Jul 8;28(1):104116.e4. https://doi.org/10.1016/j.chom.2020.05.00210.1016/j.chom.2020.05.002726322732485165Search in Google Scholar

Gupta N, Singh PK, Revankar SG, Chandrasekar PH, Kumar A. Pathobiology of Aspergillus fumigatus endophthalmitis in immunocompetent and immunocompromised mice. Microorganisms. 2019 Aug 28;7(9):297. https://doi.org/10.3390/microorganisms7090297GuptaNSinghPKRevankarSGChandrasekarPHKumarA. Pathobiology of Aspergillus fumigatus endophthalmitis in immunocompetent and immunocompromised mice. Microorganisms.2019Aug 28;7(9):297. https://doi.org/10.3390/microorganisms709029710.3390/microorganisms7090297678092231466325Search in Google Scholar

Hoenigl M, Prattes J, Neumeister P, Wölfler A, Krause R. Real-world challenges and unmet needs in the diagnosis and treatment of suspected invasive pulmonary aspergillosis in patients with haematological diseases: An illustrative case study. Mycoses. 2018 Mar; 61(3):201–205. https://doi.org/10.1111/myc.12727HoeniglMPrattesJNeumeisterPWölflerAKrauseR. Real-world challenges and unmet needs in the diagnosis and treatment of suspected invasive pulmonary aspergillosis in patients with haematological diseases: An illustrative case study. Mycoses.2018Mar; 61(3):201205. https://doi.org/10.1111/myc.1272710.1111/myc.1272729112326Search in Google Scholar

Jović Z, Janković SM, Ružić Zečević D, Milovanović D, Stefanović S, Folić M, Milovanović J, Kostić M. Clinical pharmacokinetics of second-generation triazoles for the treatment of invasive aspergillosis and candidiasis. Eur J Drug Metab Pharmacokinet. 2019 Apr; 44(2):139–157. https://doi.org/10.1007/s13318-018-0513-7JovićZJankovićSMRužić ZečevićDMilovanovićDStefanovićSFolićMMilovanovićJKostićM. Clinical pharmacokinetics of second-generation triazoles for the treatment of invasive aspergillosis and candidiasis. Eur J Drug Metab Pharmacokinet.2019Apr; 44(2):139157. https://doi.org/10.1007/s13318-018-0513-710.1007/s13318-018-0513-730284178Search in Google Scholar

Khan MA, Ali ZS, Sweezey N, Grasemann H, Palaniyar N. Progression of cystic fibrosis lung disease from childhood to adulthood: neutrophils, neutrophil extracellular trap (NET) formation, and NET degradation. Genes (Basel). 2019 Feb 26;10(3):183. https://doi.org/10.3390/genes10030183KhanMAAliZSSweezeyNGrasemannHPalaniyarN. Progression of cystic fibrosis lung disease from childhood to adulthood: neutrophils, neutrophil extracellular trap (NET) formation, and NET degradation. Genes (Basel).2019Feb 26;10(3):183. https://doi.org/10.3390/genes1003018310.3390/genes10030183647157830813645Search in Google Scholar

Khani S, Seyedjavadi SS, Hosseini HM, Goudarzi M, Valadbeigi S, Khatami S, Ajdary S, Eslamifar A, Amani J, Imani Fooladi AA, et al. Effects of the antifungal peptide Skh-AMP1 derived from Satureja khuzistanica on cell membrane permeability, ROS production, and cell morphology of conidia and hyphae of Aspergillus fumigatus. Peptides. 2020 Jan;123:170195. https://doi.org/10.1016/j.peptides.2019.170195KhaniSSeyedjavadiSSHosseiniHMGoudarziMValadbeigiSKhatamiSAjdarySEslamifarAAmaniJImani FooladiAA. Effects of the antifungal peptide Skh-AMP1 derived from Satureja khuzistanica on cell membrane permeability, ROS production, and cell morphology of conidia and hyphae of Aspergillus fumigatus. Peptides.2020Jan;123:170195. https://doi.org/10.1016/j.peptides.2019.17019510.1016/j.peptides.2019.17019531704210Search in Google Scholar

Krüger T, Luo T, Schmidt H, Shopova I, Kniemeyer O. Challenges and strategies for proteome analysis of the interaction of human pathogenic fungi with host immune cells. Proteomes. 2015 Dec 14;3(4):467–495. https://doi.org/10.3390/proteomes3040467KrügerTLuoTSchmidtHShopovaIKniemeyerO. Challenges and strategies for proteome analysis of the interaction of human pathogenic fungi with host immune cells. Proteomes.2015Dec 14;3(4):467495. https://doi.org/10.3390/proteomes304046710.3390/proteomes3040467521739028248281Search in Google Scholar

Latgé JP, Chamilos G. Aspergillus fumigatus and aspergillosis in 2019. Clin Microbiol Rev. 2019 Nov 13;33(1):e00140–18. https://doi.org/10.1128/CMR.00140-18LatgéJPChamilosG. Aspergillus fumigatus and aspergillosis in 2019. Clin Microbiol Rev.2019Nov 13;33(1):e0014018. https://doi.org/10.1128/CMR.00140-1810.1128/CMR.00140-18686000631722890Search in Google Scholar

Levitz SM. Aspergillus vaccines: hardly worth studying or worthy of hard study? Med Mycol. 2017 Jan 01;55(1):103–108. https://doi.org/10.1093/mmy/myw081LevitzSM. Aspergillus vaccines: hardly worth studying or worthy of hard study?Med Mycol.2017Jan 01;55(1):103108. https://doi.org/10.1093/mmy/myw08110.1093/mmy/myw081516659027639242Search in Google Scholar

Li T, Zhang Z, Li X, Dong G, Zhang M, Xu Z, Yang J. Neutrophil extracellular traps: signaling properties and disease relevance. Mediators Inflamm. 2020 Jul 28;2020:1–14. https://doi.org/10.1155/2020/9254087LiTZhangZLiXDongGZhangMXuZYangJ. Neutrophil extracellular traps: signaling properties and disease relevance. Mediators Inflamm.2020Jul 28;2020:114. https://doi.org/10.1155/2020/925408710.1155/2020/9254087740702032774152Search in Google Scholar

Li W, Yan J, Yu Y. Geometrical reorganization of Dectin-1 and TLR2 on single phagosomes alters their synergistic immune signaling. Proc Natl Acad Sci USA. 2019 Dec 10;116(50):25106–25114. https://doi.org/10.1073/pnas.1909870116LiWYanJYuY. Geometrical reorganization of Dectin-1 and TLR2 on single phagosomes alters their synergistic immune signaling. Proc Natl Acad Sci USA.2019Dec 10;116(50):2510625114. https://doi.org/10.1073/pnas.190987011610.1073/pnas.1909870116691117731754039Search in Google Scholar

Liedke SC, Miranda DZ, Gomes KX, Gonçalves JLS, Frases S, Nosanchuk JD, Rodrigues ML, Nimrichter L, Peralta JM, Guimarães AJ. Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers. Sci Rep. 2017 Dec;7(1):12187. https://doi.org/10.1038/s41598-017-12540-yLiedkeSCMirandaDZGomesKXGonçalvesJLSFrasesSNosanchukJDRodriguesMLNimrichterLPeraltaJMGuimarãesAJ. Characterization of the antifungal functions of a WGA-Fc (IgG2a) fusion protein binding to cell wall chitin oligomers. Sci Rep.2017Dec;7(1):12187. https://doi.org/10.1038/s41598-017-12540-y10.1038/s41598-017-12540-y561027228939893Search in Google Scholar

Liu C, Wang M, Sun W, Cai F, Geng S, Su X, Shi Y. PU.1 serves a critical role in the innate defense against Aspergillus fumigatus via dendritic cell-associated C-type lectin receptor-1 and Toll-like receptors-2 and 4 in THP-1-derived macrophages. Mol Med Rep. 2017 Jun;15(6):4084–4092. https://doi.org/10.3892/mmr.2017.6504LiuCWangMSunWCaiFGengSSuXShiY. PU.1 serves a critical role in the innate defense against Aspergillus fumigatus via dendritic cell-associated C-type lectin receptor-1 and Toll-like receptors-2 and 4 in THP-1-derived macrophages. Mol Med Rep.2017Jun;15(6):40844092. https://doi.org/10.3892/mmr.2017.650410.3892/mmr.2017.6504543620928440496Search in Google Scholar

Mackel JJ, Steele C. Host defense mechanisms against Aspergillus fumigatus lung colonization and invasion. Curr Opin Microbiol. 2019 Dec;52:14–19. https://doi.org/10.1016/j.mib.2019.04.003MackelJJSteeleC. Host defense mechanisms against Aspergillus fumigatus lung colonization and invasion. Curr Opin Microbiol.2019Dec;52:1419. https://doi.org/10.1016/j.mib.2019.04.00310.1016/j.mib.2019.04.003685852031103956Search in Google Scholar

Masaki K, Fukunaga K, Matsusaka M, Kabata H, Tanosaki T, Mochimaru T, Kamatani T, Ohtsuka K, Baba R, Ueda S, et al. Characteristics of severe asthma with fungal sensitization. Ann Allergy Asthma Immunol. 2017 Sep;119(3):253–257. https://doi.org/10.1016/j.anai.2017.07.008MasakiKFukunagaKMatsusakaMKabataHTanosakiTMochimaruTKamataniTOhtsukaKBabaRUedaS. Characteristics of severe asthma with fungal sensitization. Ann Allergy Asthma Immunol.2017Sep;119(3):253257. https://doi.org/10.1016/j.anai.2017.07.00810.1016/j.anai.2017.07.00828801088Search in Google Scholar

Matveev AL, Krylov VB, Khlusevich YA, Baykov IK, Yashunsky DV, Emelyanova LA, Tsvetkov YE, Karelin AA, Bardashova AV, Wong SSW, et al. Novel mouse monoclonal antibodies specifically recognizing β-(1→3)-D-glucan antigen. PLoS One. 2019 Apr 25;14(4):e0215535. https://doi.org/10.1371/journal.pone.0215535MatveevALKrylovVBKhlusevichYABaykovIKYashunskyDVEmelyanovaLATsvetkovYEKarelinAABardashovaAVWongSSW. Novel mouse monoclonal antibodies specifically recognizing β-(1→3)-D-glucan antigen. PLoS One.2019Apr 25;14(4):e0215535. https://doi.org/10.1371/journal.pone.021553510.1371/journal.pone.0215535648356431022215Search in Google Scholar

Mead ME, Knowles SL, Raja HA, Beattie SR, Kowalski CH, Steenwyk JL, Silva LP, Chiaratto J, Ries LNA, Goldman GH, et al. Characterizing the pathogenic, genomic, and chemical traits of Aspergillus fischeri, a close relative of the major human fungal pathogen Aspergillus fumigatus. MSphere. 2019 Feb 20;4(1):e00018–19. https://doi.org/10.1128/mSphere.00018-19MeadMEKnowlesSLRajaHABeattieSRKowalskiCHSteenwykJLSilvaLPChiarattoJRiesLNAGoldmanGH. Characterizing the pathogenic, genomic, and chemical traits of Aspergillus fischeri, a close relative of the major human fungal pathogen Aspergillus fumigatus. MSphere.2019Feb 20;4(1):e0001819. https://doi.org/10.1128/mSphere.00018-1910.1128/mSphere.00018-19638296630787113Search in Google Scholar

Movahed E, Cheok YY, Tan GMY, Lee CYQ, Cheong HC, Velayuthan RD, Tay ST, Chong PP, Wong WF, Looi CY. Lung-infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection. BMC Immunol. 2018 Dec;19(1):32. https://doi.org/10.1186/s12865-018-0269-5MovahedECheokYYTanGMYLeeCYQCheongHCVelayuthanRDTaySTChongPPWongWFLooiCY. Lung-infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection. BMC Immunol.2018Dec;19(1):32. https://doi.org/10.1186/s12865-018-0269-510.1186/s12865-018-0269-5622569530409128Search in Google Scholar

Muszewska A, Piłsyk S, Perlińska-Lenart U, Kruszewska JS. Diversity of cell wall related proteins in human pathogenic fungi. J Fungi (Basel). 2017 Dec 29;4(1):6. https://doi.org/10.3390/jof4010006MuszewskaAPiłsykSPerlińska-LenartUKruszewskaJS. Diversity of cell wall related proteins in human pathogenic fungi. J Fungi (Basel).2017Dec 29;4(1):6. https://doi.org/10.3390/jof401000610.3390/jof4010006587230929371499Search in Google Scholar

Muthu V, Sehgal IS, Dhooria S, Aggarwal AN, Agarwal R. Utility of recombinant Aspergillus fumigatus antigens in the diagnosis of allergic bronchopulmonary aspergillosis: A systematic review and diagnostic test accuracy meta-analysis. Clin Exp Allergy. 2018 Sep; 48(9):1107–1136. https://doi.org/10.1111/cea.13216MuthuVSehgalISDhooriaSAggarwalANAgarwalR. Utility of recombinant Aspergillus fumigatus antigens in the diagnosis of allergic bronchopulmonary aspergillosis: A systematic review and diagnostic test accuracy meta-analysis. Clin Exp Allergy.2018Sep; 48(9):11071136. https://doi.org/10.1111/cea.1321610.1111/cea.1321629927507Search in Google Scholar

Namvar S, Warn P, Farnell E, Bromley M, Fraczek M, Bowyer P, Herrick S. Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model. Clin Exp Allergy. 2015 May;45(5):982–993. https://doi.org/10.1111/cea.12426NamvarSWarnPFarnellEBromleyMFraczekMBowyerPHerrickS. Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model. Clin Exp Allergy.2015May;45(5):982993. https://doi.org/10.1111/cea.1242610.1111/cea.1242625270353Search in Google Scholar

Orciuolo E, Stanzani M, Canestraro M, Galimberti S, Carulli G, Lewis R, Petrini M, Komanduri KV. Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human neutrophils: implications for the pathogenesis of invasive aspergillosis. J Leukoc Biol. 2007 Oct;82(4):839–848. https://doi.org/10.1189/jlb.0207090OrciuoloEStanzaniMCanestraroMGalimbertiSCarulliGLewisRPetriniMKomanduriKV. Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human neutrophils: implications for the pathogenesis of invasive aspergillosis. J Leukoc Biol.2007Oct;82(4):839848. https://doi.org/10.1189/jlb.020709010.1189/jlb.020709017626149Search in Google Scholar

Pagano L, Busca A, Candoni A, Cattaneo C, Cesaro S, Fanci R, Nadali G, Potenza L, Russo D, Tumbarello M, et al.; SEIFEM (Sorveglianza Epidemiologica Infezioni Fungine nelle Emopatie Maligne) Group. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations. Blood Rev. 2017 Mar;31(2):17–29. https://doi.org/10.1016/j.blre.2016.09.002PaganoLBuscaACandoniACattaneoCCesaroSFanciRNadaliGPotenzaLRussoDTumbarelloM; SEIFEM (Sorveglianza Epidemiologica Infezioni Fungine nelle Emopatie Maligne) Group. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations. Blood Rev.2017Mar;31(2):1729. https://doi.org/10.1016/j.blre.2016.09.00210.1016/j.blre.2016.09.00227682882Search in Google Scholar

Pathakumari B, Liang G, Liu W. Immune defence to invasive fungal infections: A comprehensive review. Biomed Pharmacother. 2020 Oct;130:110550. https://doi.org/10.1016/j.biopha.2020.110550PathakumariBLiangGLiuW. Immune defence to invasive fungal infections: A comprehensive review. Biomed Pharmacother.2020Oct;130:110550. https://doi.org/10.1016/j.biopha.2020.11055010.1016/j.biopha.2020.11055032739740Search in Google Scholar

Paulovičová L, Paulovičová E, Farkaš P, Čížová A, Bystrický P, Jančinová V, Turánek J, Pericolini E, Gabrielli E, Vecchiarelli A, et al. Bioimmunological activities of Candida glabrata cellular mannan. FEMS Yeast Res. 2019 Mar 01;19(2):19. https://doi.org/10.1093/femsyr/foz009PaulovičováLPaulovičováEFarkašPČížováABystrickýPJančinováVTuránekJPericoliniEGabrielliEVecchiarelliA. Bioimmunological activities of Candida glabrata cellular mannan. FEMS Yeast Res.2019Mar 01;19(2):19. https://doi.org/10.1093/femsyr/foz00910.1093/femsyr/foz00930689830Search in Google Scholar

Paulussen C, Hallsworth JE, Álvarez-Pérez S, Nierman WC, Hamill PG, Blain D, Rediers H, Lievens B. Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. Microb Biotechnol. 2017 Mar; 10(2):296–322. https://doi.org/10.1111/1751-7915.12367PaulussenCHallsworthJEÁlvarez-PérezSNiermanWCHamillPGBlainDRediersHLievensB. Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. Microb Biotechnol.2017Mar; 10(2):296322. https://doi.org/10.1111/1751-7915.1236710.1111/1751-7915.12367532881027273822Search in Google Scholar

Pérez-Cantero A, Serrano DR, Navarro-Rodríguez P, Schätzlein AG, Uchegbu IF, Torrado JJ, Capilla J. Increased efficacy of oral fixed-dose combination of amphotericin B and AHCC® natural adjuvant against aspergillosis. Pharmaceutics. 2019 Sep 03; 11(9):456. https://doi.org/10.3390/pharmaceutics11090456Pérez-CanteroASerranoDRNavarro-RodríguezPSchätzleinAGUchegbuIFTorradoJJCapillaJ. Increased efficacy of oral fixed-dose combination of amphotericin B and AHCC® natural adjuvant against aspergillosis. Pharmaceutics.2019Sep 03; 11(9):456. https://doi.org/10.3390/pharmaceutics1109045610.3390/pharmaceutics11090456678130331484389Search in Google Scholar

Pfannenstiel BT, Zhao X, Wortman J, Wiemann P, Throckmorton K, Spraker JE, Soukup AA, Luo X, Lindner DL, Lim FY, et al. Revitalization of a forward genetic screen identifies three new regulators of fungal secondary metabolism in the genus Aspergillus. MBio. 2017 Nov 08;8(5):e01246–17. https://doi.org/10.1128/mBio.01246-17PfannenstielBTZhaoXWortmanJWiemannPThrockmortonKSprakerJESoukupAALuoXLindnerDLLimFY. Revitalization of a forward genetic screen identifies three new regulators of fungal secondary metabolism in the genus Aspergillus. MBio.2017Nov 08;8(5):e0124617. https://doi.org/10.1128/mBio.01246-1710.1128/mBio.01246-17558791228874473Search in Google Scholar

Ravindran M, Khan MA, Palaniyar N. Neutrophil extracellular trap formation: physiology, pathology, and pharmacology. Biomolecules. 2019 Aug 14;9(8):365. https://doi.org/10.3390/biom9080365RavindranMKhanMAPalaniyarN. Neutrophil extracellular trap formation: physiology, pathology, and pharmacology. Biomolecules.2019Aug 14;9(8):365. https://doi.org/10.3390/biom908036510.3390/biom9080365672278131416173Search in Google Scholar

Ruiz-Herrera J, Ortiz-Castellanos L. Cell wall glucans of fungi. A review. The Cell Surface. 2019 Dec;5:100022. https://doi.org/10.1016/j.tcsw.2019.100022Ruiz-HerreraJOrtiz-CastellanosL. Cell wall glucans of fungi. A review. The Cell Surface.2019Dec;5:100022. https://doi.org/10.1016/j.tcsw.2019.10002210.1016/j.tcsw.2019.100022738956232743138Search in Google Scholar

Sato S, Tamai Y. Cutaneous aspergillosis disseminated from invasive pulmonary aspergillosis. Int J Infect Dis. 2019 Oct;87:13–14. https://doi.org/10.1016/j.ijid.2019.08.005SatoSTamaiY. Cutaneous aspergillosis disseminated from invasive pulmonary aspergillosis. Int J Infect Dis.2019Oct;87:1314. https://doi.org/10.1016/j.ijid.2019.08.00510.1016/j.ijid.2019.08.00531401202Search in Google Scholar

Schlam D, Canton J, Carreño M, Kopinski H, Freeman SA, Grinstein S, Fairn GD. Gliotoxin suppresses macrophage immune function by subverting phosphatidylinositol 3,4,5-trisphosphate homeostasis. MBio. 2016 May 04;7(2):e02242–15. https://doi.org/10.1128/mBio.02242-15SchlamDCantonJCarreñoMKopinskiHFreemanSAGrinsteinSFairnGD. Gliotoxin suppresses macrophage immune function by subverting phosphatidylinositol 3,4,5-trisphosphate homeostasis. MBio.2016May 04;7(2):e0224215. https://doi.org/10.1128/mBio.02242-1510.1128/mBio.02242-15481726627048806Search in Google Scholar

Schmidt S, Tramsen L, Lehrnbecher T. Natural killer cells in antifungal immunity. Front Immunol. 2017 Nov 22;8:1623. https://doi.org/10.3389/fimmu.2017.01623SchmidtSTramsenLLehrnbecherT. Natural killer cells in antifungal immunity. Front Immunol.2017Nov 22;8:1623. https://doi.org/10.3389/fimmu.2017.0162310.3389/fimmu.2017.01623570264129213274Search in Google Scholar

Schoen TJ, Rosowski EE, Knox BP, Bennin D, Keller NP, Huttenlocher A. Neutrophil phagocyte oxidase activity controls invasive fungal growth and inflammation in zebrafish. J Cell Sci. 2019 Dec 20;133(5):133. https://doi.org/10.1242/jcs.236539SchoenTJRosowskiEEKnoxBPBenninDKellerNPHuttenlocherA. Neutrophil phagocyte oxidase activity controls invasive fungal growth and inflammation in zebrafish. J Cell Sci.2019Dec 20;133(5):133. https://doi.org/10.1242/jcs.23653910.1242/jcs.236539705536631722976Search in Google Scholar

Schülke S. Induction of interleukin-10 producing dendritic cells as a tool to suppress allergen-specific T helper 2 responses. Front Immunol. 2018 Mar 19;9:455. https://doi.org/10.3389/fimmu.2018.00455SchülkeS. Induction of interleukin-10 producing dendritic cells as a tool to suppress allergen-specific T helper 2 responses. Front Immunol.2018Mar 19;9:455. https://doi.org/10.3389/fimmu.2018.0045510.3389/fimmu.2018.00455586730029616018Search in Google Scholar

Shen Q, Zhou W, Li H, Hu L, Mo H. ROS involves the fungicidal actions of thymol against spores of Aspergillus flavus via the induction of nitric oxide. PLoS One. 2016 May 19;11(5):e0155647. https://doi.org/10.1371/journal.pone.0155647ShenQZhouWLiHHuLMoH. ROS involves the fungicidal actions of thymol against spores of Aspergillus flavus via the induction of nitric oxide. PLoS One.2016May 19;11(5):e0155647. https://doi.org/10.1371/journal.pone.015564710.1371/journal.pone.0155647487299727196096Search in Google Scholar

Shenoy MK, Iwai S, Lin DL, Worodria W, Ayakaka I, Byanyima P, Kaswabuli S, Fong S, Stone S, Chang E, et al. Immune response and mortality risk relate to distinct lung microbiomes in patients with HIV and pneumonia. Am J Respir Crit Care Med. 2017 Jan; 195(1):104–114. https://doi.org/10.1164/rccm.201603-0523OCShenoyMKIwaiSLinDLWorodriaWAyakakaIByanyimaPKaswabuliSFongSStoneSChangE. Immune response and mortality risk relate to distinct lung microbiomes in patients with HIV and pneumonia. Am J Respir Crit Care Med.2017Jan; 195(1):104114. https://doi.org/10.1164/rccm.201603-0523OC10.1164/rccm.201603-0523OC521491827447987Search in Google Scholar

Shishodia SK, Tiwari S, Shankar J. Resistance mechanism and proteins in Aspergillus species against antifungal agents. Mycology. 2019 Jul 03;10(3):151–165. https://doi.org/10.1080/21501203.2019.1574927ShishodiaSKTiwariSShankarJ. Resistance mechanism and proteins in Aspergillus species against antifungal agents. Mycology.2019Jul 03;10(3):151165. https://doi.org/10.1080/21501203.2019.157492710.1080/21501203.2019.1574927669178431448149Search in Google Scholar

Shopova IA, Belyaev I, Dasari P, Jahreis S, Stroe MC, Cseresnyés Z, Zimmermann AK, Medyukhina A, Svensson CM, Krüger T, et al. Human neutrophils produce antifungal extracellular vesicles against Aspergillus fumigatus. MBio. 2020 Apr 14;11(2):e00596–20. https://doi.org/10.1128/mBio.00596-20ShopovaIABelyaevIDasariPJahreisSStroeMCCseresnyésZZimmermannAKMedyukhinaASvenssonCMKrügerT. Human neutrophils produce antifungal extracellular vesicles against Aspergillus fumigatus. MBio.2020Apr 14;11(2):e0059620. https://doi.org/10.1128/mBio.00596-2010.1128/mBio.00596-20715782032291301Search in Google Scholar

Smole U, Kratzer B, Pickl WF. Soluble pattern recognition molecules: guardians and regulators of homeostasis at airway mucosal surfaces. Eur J Immunol. 2020 May;50(5):624–642. https://doi.org/10.1002/eji.201847811SmoleUKratzerBPicklWF. Soluble pattern recognition molecules: guardians and regulators of homeostasis at airway mucosal surfaces. Eur J Immunol.2020May;50(5):624642. https://doi.org/10.1002/eji.20184781110.1002/eji.201847811721699232246830Search in Google Scholar

Souza JAM, Baltazar LM, Carregal VM, Gouveia-Eufrasio L, de Oliveira AG, Dias WG, Campos Rocha M, Rocha de Miranda K, Malavazi I, Santos DA, et al. Characterization of Aspergillus fumigatus extracellular vesicles and their effects on macrophages and neutrophils functions. Front Microbiol. 2019 Sep 4;10:2008. https://doi.org/10.3389/fmicb.2019.02008SouzaJAMBaltazarLMCarregalVMGouveia-EufrasioLde OliveiraAGDiasWGCampos RochaMRocha de MirandaKMalavaziISantosDA. Characterization of Aspergillus fumigatus extracellular vesicles and their effects on macrophages and neutrophils functions. Front Microbiol.2019Sep 4;10:2008. https://doi.org/10.3389/fmicb.2019.0200810.3389/fmicb.2019.02008673816731551957Search in Google Scholar

Takazono T, Izumikawa K. Recent advances in diagnosing chronic pulmonary aspergillosis. Front Microbiol. 2018 Aug 17;9:1810. https://doi.org/10.3389/fmicb.2018.01810TakazonoTIzumikawaK. Recent advances in diagnosing chronic pulmonary aspergillosis. Front Microbiol.2018Aug 17;9:1810. https://doi.org/10.3389/fmicb.2018.0181010.3389/fmicb.2018.01810610779030174658Search in Google Scholar

Tsunawaki S, Yoshida LS, Nishida S, Kobayashi T, Shimoyama T. Fungal metabolite gliotoxin inhibits assembly of the human respiratory burst NADPH oxidase. Infect Immun. 2004 Jun;72(6):3373–3382. https://doi.org/10.1128/IAI.72.6.3373-3382.2004TsunawakiSYoshidaLSNishidaSKobayashiTShimoyamaT. Fungal metabolite gliotoxin inhibits assembly of the human respiratory burst NADPH oxidase. Infect Immun.2004Jun;72(6):33733382. https://doi.org/10.1128/IAI.72.6.3373-3382.200410.1128/IAI.72.6.3373-3382.200441571015155643Search in Google Scholar

Ulrich S, Ebel F. Monoclonal antibodies as tools to combat fungal infections. J Fungi (Basel). 2020 Feb 04;6(1):22. https://doi.org/10.3390/jof6010022UlrichSEbelF. Monoclonal antibodies as tools to combat fungal infections. J Fungi (Basel).2020Feb 04;6(1):22. https://doi.org/10.3390/jof601002210.3390/jof6010022715120632033168Search in Google Scholar

Upadhya R, Lam WC, Maybruck B, Specht CA, Levitz SM, Lodge JK. Induction of protective immunity to cryptococcal infection in mice by a heat-killed, chitosan-deficient strain of Cryptococcus neoformans. MBio. 2016 Jul 06;7(3):e00547–16. https://doi.org/10.1128/mBio.00547-16UpadhyaRLamWCMaybruckBSpechtCALevitzSMLodgeJK. Induction of protective immunity to cryptococcal infection in mice by a heat-killed, chitosan-deficient strain of Cryptococcus neoformans. MBio.2016Jul 06;7(3):e0054716. https://doi.org/10.1128/mBio.00547-1610.1128/mBio.00547-16495965227165801Search in Google Scholar

van de Peppel RJ, Visser LG, Dekkers OM, de Boer MGJ. The burden of invasive aspergillosis in patients with haematological malignancy: A meta-analysis and systematic review. J Infect. 2018 Jun;76(6):550–562. https://doi.org/10.1016/j.jinf.2018.02.012van de PeppelRJVisserLGDekkersOMde BoerMGJ. The burden of invasive aspergillosis in patients with haematological malignancy: A meta-analysis and systematic review. J Infect.2018Jun;76(6):550562. https://doi.org/10.1016/j.jinf.2018.02.01210.1016/j.jinf.2018.02.01229727605Search in Google Scholar

van de Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latgé JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol. 2017 Nov;15(11):661–674. https://doi.org/10.1038/nrmicro.2017.90van de VeerdonkFLGresnigtMSRomaniLNeteaMGLatgéJP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol.2017Nov;15(11):661674. https://doi.org/10.1038/nrmicro.2017.9010.1038/nrmicro.2017.9028919635Search in Google Scholar

Wagener J, Echtenacher B, Rohde M, Kotz A, Krappmann S, Heesemann J, Ebel F. The putative alpha-1,2-mannosyltransferase AfMnt1 of the opportunistic fungal pathogen Aspergillus fumigatus is required for cell wall stability and full virulence. Eukaryot Cell. 2008 Oct;7(10):1661–1673. https://doi.org/10.1128/EC.00221-08WagenerJEchtenacherBRohdeMKotzAKrappmannSHeesemannJEbelF. The putative alpha-1,2-mannosyltransferase AfMnt1 of the opportunistic fungal pathogen Aspergillus fumigatus is required for cell wall stability and full virulence. Eukaryot Cell.2008Oct;7(10):16611673. https://doi.org/10.1128/EC.00221-0810.1128/EC.00221-08256806218708564Search in Google Scholar

Wang F, Zhang C, Jiang Y, Kou C, Kong Q, Long N, Lu L, Sang H. Innate and adaptive immune response to chronic pulmonary infection of hyphae of Aspergillus fumigatus in a new murine model. J Med Microbiol. 2017 Oct 01;66(10):1400–1408. https://doi.org/10.1099/jmm.0.000590WangFZhangCJiangYKouCKongQLongNLuLSangH. Innate and adaptive immune response to chronic pulmonary infection of hyphae of Aspergillus fumigatus in a new murine model. J Med Microbiol.2017Oct 01;66(10):14001408. https://doi.org/10.1099/jmm.0.00059010.1099/jmm.0.00059028923131Search in Google Scholar

Wang Y, Wang K, Masso-Silva JA, Rivera A, Xue C. A Heat-Killed Cryptococcus mutant strain induces host protection against multiple invasive mycoses in a murine vaccine model. MBio. 2019 Nov 26;10(6):e02145–19. https://doi.org/10.1128/mBio.02145-19WangYWangKMasso-SilvaJARiveraAXueC. A Heat-Killed Cryptococcus mutant strain induces host protection against multiple invasive mycoses in a murine vaccine model. MBio.2019Nov 26;10(6):e0214519. https://doi.org/10.1128/mBio.02145-1910.1128/mBio.02145-19687971731772051Search in Google Scholar

Woo PCY, Lau SKP, Lau CCY, Tung ETK, Au-Yeung RKH, Cai JP, Chong KTK, Sze KH, Kao RY, Hao Q, et al. Mp1p homologues as virulence factors in Aspergillus fumigatus. Med Mycol. 2018 Apr 01;56(3):350–360. https://doi.org/10.1093/mmy/myx052WooPCYLauSKPLauCCYTungETKAu-YeungRKHCaiJPChongKTKSzeKHKaoRYHaoQ. Mp1p homologues as virulence factors in Aspergillus fumigatus. Med Mycol.2018Apr 01;56(3):350360. https://doi.org/10.1093/mmy/myx05210.1093/mmy/myx05228992243Search in Google Scholar

Xiao H, Tang Y, Cheng Q, Liu J, Li X. Risk prediction and prognosis of invasive fungal disease in hematological malignancies patients complicated with bloodstream infections. Cancer Manag Res. 2020 Mar;12:2167–2175. https://doi.org/10.2147/CMAR.S238166XiaoHTangYChengQLiuJLiX. Risk prediction and prognosis of invasive fungal disease in hematological malignancies patients complicated with bloodstream infections. Cancer Manag Res.2020Mar;12:21672175. https://doi.org/10.2147/CMAR.S23816610.2147/CMAR.S238166710287732273756Search in Google Scholar

Zhang C, Chen F, Liu X, Han X, Hu Y, Su X, Chen Y, Sun Y, Han L. Gliotoxin induces cofilin phosphorylation to promote actin cytoskeleton dynamics and internalization of Aspergillus fumigatus into type II human pneumocyte cells. Front Microbiol. 2019 Jun 18;10:1345. https://doi.org/10.3389/fmicb.2019.01345ZhangCChenFLiuXHanXHuYSuXChenYSunYHanL. Gliotoxin induces cofilin phosphorylation to promote actin cytoskeleton dynamics and internalization of Aspergillus fumigatus into type II human pneumocyte cells. Front Microbiol.2019Jun 18;10:1345. https://doi.org/10.3389/fmicb.2019.0134510.3389/fmicb.2019.01345659131031275272Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo