087 CARD9 promotes NLRP3-induced IL-1β production on candida albicans infection of macrophages

The downstream adaptor protein (CARD9) is a crucial signaling molecule in antifungal host defense and patients deficient CARD9 are highly susceptible to spontaneous development of systemic fungal infections, predominantly caused by Candida species. NLRP3 inflammasome cytosolic multiprotein complex composed the innate immune receptor NLRP3, adapter ASC, inflammatory protease caspase-1. Once activated, it induces pro-caspase-1 self-cleavage activation, which results maturation IL-1β proinflammatory cytokine required for control infections. However, whether can affect SYK-mediated activation production infection albicans has remained unclear. We infected murine bone marrow-derived macrophages (BMDMs) from wild type (WT) Card9-/- mice with albicans, found that mRNA expression pro-IL-1β, SYK, casepase-1 ASC were notably decreased BMDMs compared WT BMDMs. Furthermore, levels IL-1β, p-SYK, casepase-1-p10 also To evaluate affects through LPS-primed presence or absence R406 (a specific SYK inhibitor), showed was reduced both Card9-/-macrophages R406. In addition, stimulation nigericin elicited similar cell types. Taken together, these indicate promotes upregulating pro-IL-1β response infection.