IFN-gamma is required for IL-12 responsiveness in mice with Candida albicans infection.
To elucidate the role of IFN-gamma in antifungal CD4+ Th-dependent immunity, 129/Sv/Ev mice deficient for IFN-gamma receptor (IFN-gammaR(-/-)) were assessed for susceptibility to gastrointestinal or systemic Candida albicans infection and for parameters of innate and adaptive T helper immunity. IFN-gammaR(-/-) mice failed to mount protective Th1-mediated acquired immunity upon mucosal immunization or in response to a live vaccine strain of the yeast. The impaired Th1-mediated resistance correlated with defective IL-12 responsiveness, but not IL-12 production, and occurred in the presence of an increased innate antifungal resistance. The development of nonprotective Th2 responses was observed in IFN-gammaR(-/-) mice upon mucosal infection and subsequent reinfection. However, under experimental conditions of Th2 cell activation, the occurrence of Th2 cell responses was similar in IFN-gammaR(-/-) and in IFN-gammaR(+/+) mice. These results indicate the complex immunoregulatory role of IFN-gamma in the induction of mucosal and nonmucosal anticandidal Th cell responses; IFN-gamma is not essential for the occurrence of Th2 responses but is required for development of IL-12-dependent protective Th1-dependent immunity.
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
E
E
Cenci
A
A
Mencacci
G
G
Del Sero
C F
CF
d'Ostiani
P
P
Mosci
A
A
Bacci
C
C
Montagnoli
M
M
Kopf
L
L
Romani
D000818:Animals; D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004198:Disease Susceptibility; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012008:Recurrence; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D018664:Interleukin-12; D007371:Interferon-gamma