Malassezia spp. induce inflammatory cytokines and activate NLRP3 inflammasomes in phagocytes

Malasseziaspp. are common eukaryotic yeasts that colonize mammalian skin. Recently, the authors and others have observed thatMalassezia globosaandMalassezia restrictacan be found in the intestines in the context of certain diseases, including Crohn's disease and pancreatic cancer. In order to better understand the nature of innate inflammatory responses to these yeasts, inflammatory responses induced byM. restrictaandM. globosain mouse bone marrow-derived M phi s (BMDM) and dendritic cells (BMDC) are evaluated. WhileMalasseziayeasts induce proinflammatory cytokine production from both M phi s and dendritic cells, the levels of production from BMDC were more pronounced. BothM. restrictaandM. globosaactivated inflammatory cytokine production from BMDC in large part through Dectin2 and CARD9 signaling, although additional receptors appear to be involved in phagocytosis and activation of reactive oxygen production in response to the yeasts. BothM. restrictaand M. globosastimulate production of pro-IL-1 beta as well as activation of the NLRP3 inflammasome. NLRP3 inflammasome activation byMalasseziafungi requires SYK signaling, potassium efflux and actin rearrangement. Together, the data further the understanding of the coordinated involvement of multiple innate immune receptors in recognizingMalassezia globosaandMalassezia restrictaand orchestrating phagocyte inflammatory and antimicrobial responses.

Automated summary

Malassezia spp. yeasts are commonly found on mammalian skin, but can also be found in the intestines in certain diseases. They induce inflammatory responses by activating proinflammatory cytokine production, mainly through the Dectin2 and CARD9 signaling pathways, and stimulate NLRP3 inflammasome activation.