Increased resistance to systemic candidiasis in athymic or interleukin-10-depleted mice.
Candida albicans produces a virulence-associated immunomodulatory protein (p43), which activates lymphocytes polyclonally, suppresses specific antibody responses to Candida antigens, and potentiates systemic growth of C. albicans. In this study, athymic, unlike euthymic, C57BL/6 mice were resistant to systemic candidiasis and produced lower serum levels of interleukin (IL)-4 and IL-10. Pretreatment with p43 stimulated the production of both cytokines. Depletion of IL-10, but not of IL-4, in euthymic animals reestablished resistance and abrogated p43-dependent suppression of the specific antibody response and facilitated C. albicans growth. In agreement with these results, both immunosuppression and p43-mediated facilitation of the fungus growth were abolished in IL-10 knockout mice. These observations demonstrate the relevance of IL-10 in facilitating systemic candidiasis and suggest a critical role for the immunosuppressive virulence factor p43 in the process.
Tavares
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D
Laboratory of Microbiology, Institute for Biomedical Sciences Abel Salazar, and 3Institute for Molecular and Cell Biology, Porto, Portugal.
Ferreira
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P
Arala-Chaves
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M
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002177:Candidiasis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000172:deficiency / Q000276:immunology*; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D037521:Virulence Factors
D001426:Bacterial Proteins; D008074:Lipoproteins; D037521:Virulence Factors; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma