Of all pathogenic
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
As a thermophilic fungus,
Moreover,
So far, none of the pathogenic factors is unique to
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
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
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
The elimination of the daily-inhaled conidia mainly depends on the innate immune response, but the treatment for serious
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
Although recently there is some progress published on the study of vaccines against
Currently, some
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
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
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
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
The multifactorial virulence factors and complex pathogenic mechanism of