Fas-FasL interactions modulate host defense against systemic Candida albicans infection.
Fas-FasL costimulation modulates the production of proinflammatory cytokines, and MRL/lpr mice, which lack a functional Fas molecule, produce more proinflammatory cytokines. This study found that Fas-FasL interactions are involved in host defense against lethal infection with Candida albicans. Macrophages of MRL/lpr mice produced significantly more tumor necrosis factor and 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 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, protecting mice against disseminated candidiasis.
Netea
M G
MG
Departments of Medicine, Catholic University Nijmegen, University Hospital, Nijmegen, The Netherlands.
van Der Meer
J W
JW
Meis
J F
JF
Kullberg
B J
BJ
D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D053222:Fas Ligand Protein; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor