Endogenous interleukin 4 is required for development of protective CD4+ T helper type 1 cell responses to Candida albicans.
Interleukin (IL)-4-deficient mice were used to assess susceptibility to systemic or gastrointestinal Candida albicans infections, as well as parameters of innate and elicited T helper immunity. In the early stage of systemic infection with virulent C. albicans, an unopposed interferon (IFN)-gamma response renders IL-4-deficient mice more resistant than wild-type mice to infection. Yet, IL-4-deficient mice failed to efficiently control infection in the late stage and succumbed to it. Defective IFN-gamma and IL-12 production, but not IL-12 responsiveness, was observed in IL-4-deficient mice that failed to mount protective T helper type 1 cell (Th1)-mediated acquired immunity in response to a live vaccine strain of the yeast or upon mucosal immunization in vivo. In vitro, IL-4 primed neutrophils for cytokine release, including IL-12. However, late treatment with exogenous IL-4, while improving the outcome of infection, potentiated CD4(+) Th1 responses even in the absence of neutrophils. These findings indicate that endogenous IL-4 is required for the induction of CD4(+) Th1 protective antifungal responses, possibly through the combined activity on cells of the innate and adaptive immune systems.
Mencacci
A
A
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06122 Perugia, Italy.
Del Sero
G
G
Cenci
E
E
d'Ostiani
C F
CF
Bacci
A
A
Montagnoli
C
C
Kopf
M
M
Romani
L
L
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002176:Candida albicans / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology; D007239:Infections / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000378:metabolism*
D007378:Interleukins; D009573:Nitrites; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma