Fig. 4

Tumor-associated-mycobiome regulates the physiological and immune responses of cancer through different signaling pathways. Dectin-1, Dectin-2, Dectin-3, and Mincle are CLRs that interact with Syk to activate PLCγ and then enhance the function of PKCδ that is critically involved in CARD9 phosphorylation at T231 with the aid of Vav proteins in the coiled-coil domain, allowing the formation of CBM complex (CARD9-BCL10-MALT1). The CBM complex activates NF-κB and MAPK pathways, subsequently increasing inflammatory cytokines production. CARD9 also binds with RAS-GRF-1 and H-RAS to activate ERK pathways. CARD9 can free Rac1 from LyGDI to promote ROS. Fungi induce NLRP3 inflammasome activation in MDSCs via Dectin-3, which depends on glycogen metabolism-dependent glycolysis. Fungi promote transcription of NLRP3, Pro-caspase-1, and IL-1β genes through activation of the JAK-STAT1 signaling pathway, whereas mtROS, as a second activation signal, is required for fungal-induced NLRP3 inflammasome activation. IL-1β production is regulated by two steps: transcription and maturation. Typical NF-κB first induces IL-1β into an inactive precursor called pro-IL-1β, and then pro-IL-1β is cleaved into active IL-1β by active caspase-1. SyK, spleen tyrosine kinase; PLCγ, phosphoinositide phospholipase Cγ; PKCδ, protein kinase Cδ; JAK, Janus kinase; STAT; NF-Κb, nuclear factor-κB; STAT, signal transducer and activator of transcription