Fas-FasL interactions modulate host defense against systemic Candida albicans infection

Fas-FasL costimulation modulates the production of proinflammatory cytokine s, and MRL/lpr mice, which lack a functional Fas molecule, produce more pro inflammatory cytokines. This study found that Fas-FasL interactions are inv olved in host defense against lethal infection with Candida albicans. Macro phages of MRL/lpr mice produced significantly more tumor necrosis factor an d interleukin-1 after stimulation with C. albicans than did control MRL+/macrophages. Mortality of Fas-deficient mice with disseminated candidiasis was significantly lower than control animals' because of decreased fungal l oad and inhibition of the formation of invasive hyphae in their organs. Inc reased recruitment of neutrophils at the infection site appeared to be resp onsible for these effects. In contrast, phagocytosis and killing of C. albi cans by neutrophils of MRL/lpr and MRL+/+ mice was similar. Absence of Fas- FasL interactions leads to increased cytokine production after C. albicans stimulation, protecting mice against disseminated candidiasis.