Defective co-stimulation and impaired Th1 development in tumor necrosis factor/lymphotoxin-alpha double-deficient mice infected with Candida albicans.
To define the immunological functions of tumor necrosis factor (TNF) in Candida albicans infection, TNF/lymphotoxin (LT)-alpha double-deficient mice were assessed for susceptibility to systemic or gastrointestinal infection and parameters of innate and adaptive Th immunity. When compared to wild-type mice, TNF/LT-alpha-deficient mice were more susceptible to either type of infection caused by virulent or low-virulence C. albicans cells. Susceptibility to infection correlated with impaired development of protective Th1 responses, in spite of the production of bioactive IL-12. The occurrence of predominant Th2 responses was associated with both impaired antifungal effector functions of neutrophils and a defective expression of co-stimulatory molecules on macrophages. All functions were improved upon administration of recombinant TNF-alpha, also resulting in increased resistance to infection. These findings indicate that the protective effect of TNF-alpha in candidiasis relies on the induction of antifungal Th1 responses, possibly occurring through stimulation of antifungal effector functions and co-stimulatory activities of phagocytic cells.
Mencacci
A
A
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Cenci
E
E
Del Sero
G
G
Fè d'Ostiani
C
C
Mosci
P
P
Montagnoli
C
C
Bacci
A
A
Bistoni
F
F
Quesniaux
V F
VF
Ryffel
B
B
Romani
L
L
D000818:Animals; D002177:Candidiasis / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D005767:Gastrointestinal Diseases / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000276:immunology
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha