Cytosolic receptors and signaling in antifungal immunity.

The host innate immune system provides the first line of protection against invading microbial pathogens, including fungi. Recognition of fungi by host pattern-recognition receptors (PRRs) is critical for their clearance. PRRs bind to pathogen-associated molecular patterns (PAMPs) that can be present on the fungal surface, secreted by them, or found in their genetic material, but also damage-associated molecular patterns (DAMPs) released by host cells as a result of fungal infection. These receptors can be located at the cell surface, the endosome, or in the cytosol of host cells. Depending on PRR location and the nature of the molecular patterns (PAMPs/DAMPs) they recognize, their activation induces specific signaling pathways culminating in tailored immune responses. There are two families of innate immune receptors that can principally sense fungi, namely membrane-bound Toll-like receptors (TLRs) and C-type lectin receptors (CLRs). In addition, as phagocytosed fungal pathogens can escape the phagolysosome and reach the cytoplasm, cytosolic sensors such as Nod-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are also important in fungal sensing and play essential roles in antifungal host protection. This review summarizes the cytosolic receptors and the signaling pathways involved in antifungal innate immunity.