The Host’s Innate Immune Response to Pathogenic Candida albicans and Other Fungal Pathogens

Pathogenic fungi such as Candida albicans and Aspergillus fumigatus, like many other microbial pathogens, evade killing by the host complement system by controlling the action of complement and by exploiting host regulators and inhibitors. The human complement system is the first line of defense against fungal and microbial pathogens. This system can discriminate between self and non-self. Once activated, it is highly efficient in killing and eliminating microbes. Many fungal complement evasion proteins are moonlighting proteins and are involved in basic metabolic reactions such as glycolysis. These fungal moonlighting proteins have metabolic functions in the cytoplasm. However, as cell surfaces are exposed and as secreted proteins, they display complement and immune evasion functions. Here, we review the multiple and often redundant functions of fungal moonlighting proteins from Candida albicans and Aspergillus fumigatus in acquiring human soluble immune regulators and interacting with cellular receptors. We also describe the role of microRNAs and macrovesicles in the immune battle of fungal pathogens with their human host. The identification and functional characterization of fungal immune evasion proteins is the basis for the identification of new candidates for immune targeting.