Pathogenic fungi cause a wide range of syndromes in immune-competent and immune-compromised individuals, with life-threatening disease primarily seen in humans with HIV/AIDS and in patients receiving immunosuppressive therapies for cancer, autoimmunity, and end-organ failure. The discovery that specific primary immune deficiencies manifest with fungal infections and the development of animal models of mucosal and invasive mycoses have facilitated insight into fungus-specific recognition, signaling, effector pathways, and adaptive immune responses. Progress in deciphering the molecular and cellular basis of immunity against fungi is guiding preclinical studies into vaccine and immune reconstitution strategies for vulnerable patient groups. Furthermore, recent work has begun to address the role of endogenous fungal communities in human health and disease. In this review, we summarize a contemporary understanding of protective immunity against fungi.
Michail S. Lionakis, Iliyan D. Iliev, Tobias M. Hohl
Model of fungus-induced CLR signaling in antifungal defense.
At the site of inoculation, particulate fungal polysaccharides bind C-type lectin receptors (CLRs) and Fc receptors (FcRs), resulting in SYK activation via ITAM signaling in the receptor tail, the FcRγ signaling adaptor, or integrin receptor activation. The ensuing PKCδ and CARD9 activation is critical for caspase-1 and caspase-8 activity, MAP kinase signaling (not shown), NF-κB activation, and cytokine production. SYK-dependent PLCγ2 activation is linked to NADPH oxidase assembly and calcineurin-dependent NFAT activation. Dectin/SYK signaling controls IRF5-dependent IFN-γ production. VAV1 and BTK can interact with dectin-1 to mediate phagocytosis of