Fas-FasL Interactions Modulate Host Defense against Systemic Candida albicans Infection

Fas-FasL costimulation modulates the production of proin¯ammatory cytokines, and MRL/lpr mice, which lack a functional Fas molecule, produce more proin¯ammatory cyto-kines. This study found that Fas-FasL interactions are involved in host defense against lethal infection with Candida albicans. Macrophages of MRL/lpr mice produced signi®cantly more tumor necrosis factor and interleukin-1 after stimulation with C. albicans than did control MRL+/+ macrophages. Mortality of Fas-de®cient mice with disseminated candidiasis was signi®cantly lower than control animals ' because of decreased fungal load and inhibition of the formation of invasive hyphae in their organs. Increased recruitment of neutrophils at the infection site appeared to be responsible for these effects. In contrast, phagocytosis and killing of C. albicans by neutrophils of MRL/lpr and MRL+/+ mice was similar. Absence of Fas-FasL interactions leads to increased cytokine production after C. albicans stimulation, pro-tecting mice against disseminated candidiasis. Fas (CD95) is a cell-surface antigen that belongs to a family of molecules including the tumor necrosis factor (TNF) recep-tors, nerve growth factor receptor, CD40, CD30, and OX4