ITAM Receptor Signaling and the NLRP3 Inflammasome in Antifungal Immunity

Infections with fungi can cause systemic life-threatening diseases in immunocompromised individuals like cancer or AIDS patients. Recent work has uncovered essential roles for C-type lectin pattern recognition receptors, spleen tyrosine kinase (SYK) and the cytosolic NLRP3 inflammasome in innate antifungal immunity. Upon fungal infection, SYK is activated by several ITAM-containing or ITAM-coupled C-type lectin receptors on myeloid cells leading to the production of pro-inflammatory cytokines including IL-1 beta to initiate antifungal responses. Mature IL-1 beta production requires in addition to the synthesis of pro-IL-1 beta a cleavage of the precursor protein by the inflammatory Caspase-1 which is controlled within the NLRP3 inflammasome. Here, we discuss how ITAM receptor signaling and NLRP3 cooperate for the induction of antifungal immunity.