Fonsecaea pedrosoi‐induced Th17‐cell differentiation in mice is fostered by Dectin‐2 and suppressed by Mincle recognition |
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| Authors: | Marcel Wüthrich Huafeng Wang Mengyi Li Tassanee Lerksuthirat Sarah E. Hardison Gordon D. Brown Bruce Klein |
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| Affiliation: | 1. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin‐Madison, WI, USA;2. Department of Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin‐Madison, WI, USA;3. Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin‐Madison, WI, USA;4. Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK |
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| Abstract: | Chromoblastomycosis is a chronic skin infection caused by the pigmented saprophytic mould Fonsecaea pedrosoi. Chronicity of infection can be broken by a coordinated innate recognition of the spores by pattern recognition receptors. While Mincle signaling via the Syk/Card9 pathway is required for fungal recognition by host cells, it is not sufficient for host control. Exogenously applied TLR agonists are necessary to promote the induction of proinflammatory cytokines and clearance of infection in vivo. Here, we investigated whether costimulation by TLR agonists fosters the development of adaptive immune responses, by examining the development of fungus‐specific T cells. Subcutaneous infection of mice with F. pedrosoi spores induced the activation, expansion, and differentiation of Ag‐specific CD4+ T cells but TLR costimulation did not further augment these T‐cell responses. The Dectin‐2/FcRγ/Card9 signaling pathway promoted the differentiation of fungus‐specific CD4+ T cells into Th17 cells, whereas Mincle inhibited the development of this T‐helper subset in infected mice. These results indicate differential roles for Dectin‐2 and Mincle in the generation of adaptive immune responses to F. pedrosoi infection. |
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| Keywords: | Chromoblastomycosis C‐type lectin Fungi Dectin‐2 Mincle T‐cell differentiation Th17 cell |
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