Oral Presentation Lorne Infection and Immunity 2022

Deep tissue infection by an invasive human fungal pathogen requires novel lipid-based suppression of the IL-17 response (#2)

Suzanne Noble 1
  1. University of California San Francisco, San Francisco, CALIFORNIA, United States

Candida albicans is the most common cause of human fungal infection, but the mechanisms of invasive pathogenesis remain poorly defined. Here we identify an unexpected mechanism: lipid-mediated immunosuppression. Through forward genetics, we found that C. albicans secretes a lipase, Lip2, that is critical for invasive disease. Murine infection with C. albicans strains that lack Lip2 display an exaggerated host IL-17 response that leads to fungal clearance from solid organs and host survival. IL-17 signaling is required for Lip2 action. The lipase activity of Lip2 inhibits IL-17 production indirectly through suppression of IL-23 production by tissue resident dendritic cells. We conclude that C. albicans suppresses antifungal IL-17 defense in solid organs by altering the tissue lipid milieu.