Deep tissue infection by an invasive human fungal pathogen requires lipid-based suppression of the IL-17 response
Pauline Basso, Eric V. Dang, Anatoly Urisman, Leah E. Cowen, Hiten D. Madhani, Suzanne M. Noble
Abstract
Candida albicans is the most common cause of fungal infection in humans. IL-17 is critical for defense against superficial fungal infections, but the role of this response in invasive disease is less understood. We show that C. albicans secretes a lipase, Lip2, that facilitates invasive disease via lipid-based suppression of the IL-17 response. Lip2 was identified as an essential virulence factor in a forward genetic screen in a mouse model of bloodstream infection. Murine infection with C. albicans strains lacking Lip2 display exaggerated IL-17 responses that lead to fungal clearance from solid organs and host survival. Both IL-17 signaling and lipase activity are required for Lip2-mediated suppression. Lip2 inhibits IL-17 production indirectly by suppressing IL-23 production by tissue-resident dendritic cells. The lipase hydrolysis product, palmitic acid, similarly suppresses dendritic cell activation in vitro. Thus, C. albicans suppresses antifungal IL-17 defense in solid organs by altering the tissue lipid milieu.