IL-23 and IL-17A, but Not IL-12 and IL-22, Are Required for Optimal Skin Host Defense against Candida albicans
- 1 November 2010
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 185 (9), 5453-5462
- https://doi.org/10.4049/jimmunol.1001153
Abstract
IL-23 and Th17 cells play important roles in host defense against systemic infections with extracellular bacteria and fungi, although their roles in immunity against localized skin infections are less well defined. Here, the contributions of IL-23 and Th17 cytokines in host defense against cutaneous Candida albicans infection were evaluated. Mice deficient in IL-23 or IL-17A demonstrated delayed healing and decreased IL-17A production after skin infection with C. albicans compared with wild-type mice or mice deficient in IL-12 or IL-22. Histologic examination revealed epidermal hyperplasia overlying infected dermis four days postinoculation in wild-type mice. In IL-23–deficient mice, fungal burden was greater in skin, neither IL-17A nor IL-22 mRNAs were expressed postinfection, and these mice demonstrated only minimal epidermal hyperplasia. Exogenous recombinant IL-17A injected at the site of skin infection promoted more rapid healing of candidiasis in both wild-type mice and mice deficient in IL-23 and IL-12. Taken together, these results demonstrate that IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal host defense against cutaneous candidiasis. In addition, recombinant IL-17A may serve as a potential therapy to enhance healing in individuals with chronic cutaneous candidiasis.Keywords
This publication has 44 references indexed in Scilit:
- IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in miceJCI Insight, 2010
- Human Dectin-1 Deficiency and Mucocutaneous Fungal InfectionsThe New England Journal of Medicine, 2009
- A HomozygousCARD9Mutation in a Family with Susceptibility to Fungal InfectionsThe New England Journal of Medicine, 2009
- Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infectionThe Journal of Experimental Medicine, 2009
- Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasisThe Journal of Experimental Medicine, 2009
- Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3 The Journal of Experimental Medicine, 2008
- Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)The Lancet, 2008
- Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)The Lancet, 2008
- Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndromeNature, 2008
- IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesisThe Journal of Experimental Medicine, 2006