IL-10 Is Required for Development of Protective Th1 Responses in IL-12-Deficient Mice upon Candida albicans Infection

  • Mencacci A
  • Cenci E
  • Sero G
  • et al.
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Abstract

IL-12 is both required and prognostic for Th1 development in mice with Candida albicans infection. To delineate further the physiologic role of IL-12 in antifungal immunity, mice deficient for this cytokine were assessed for susceptibility to C. albicans infections, and for parameters of innate and adaptive immunity. IL-12-deficient mice were highly susceptible to gastrointestinal infection or to reinfection and showed elevated production of Candida-specific IgE and IL-4 and defective production of IFN-γ. The failure to mount protective Th1 responses occurred despite the presence of an unimpaired innate antifungal immune response, which correlated with unaltered IFN-γ production, but defective production of, and responsiveness to, inhibitory IL-10. IL-10 or IL-12 neutralization increased the innate antifungal resistance in wild-type mice. However, in IL-12-deficient mice, treatment with exogenous IL-12 or IL-10 impaired IL-4 production and increased resistance to infection, through a negative effect on the CTLA-4/B7-2 costimulatory pathway. These results confirm the obligatory role of IL-12 in the induction of anticandidal Th1 responses, and indicate the existence of a positive regulatory loop between IL-12 and IL-10 that may adversely affect the innate antifungal response, but is required for optimal costimulation of IL-12-dependent CD4+Th1 cells.

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Mencacci, A., Cenci, E., Sero, G. D., Fé d’Ostiani, C., Mosci, P., Trinchieri, G., … Romani, L. (1998). IL-10 Is Required for Development of Protective Th1 Responses in IL-12-Deficient Mice upon Candida albicans Infection. The Journal of Immunology, 161(11), 6228–6237. https://doi.org/10.4049/jimmunol.161.11.6228

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