Fonsecaea pedrosoi-induced Th17-cell differentiation in mice is fostered by Dectin-2 and suppressed by Mincle recognition.
Bottom Line: 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.
Affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.Show MeSH
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Mentions: Engagement of Mincle on human DC by F. monophora was reported to suppress Th1 cell polarization 14. To investigate whether T‐cell differentiation was altered in response to F. pedrosoi infection, we enumerated the number and frequency of cytokine producing Ag‐specific T cells in the absence of the Myd88 and CLR/Card9 signaling axis. Card9−/−, FcRγ−/−, and Dectin‐2−/− mice showed reduced numbers and frequencies of Th17 cells (Fig. 4A–C). Although to a lesser extent, Th1‐cell differentiation was similarly impacted in the above‐mentioned recipient strains of mice. Dectin‐1−/− and Clec4d−/− mice had reduced numbers but not frequencies of Th17 and Th1 cells. Interestingly, Mincle−/− mice showed increased numbers and frequencies of Th17 but reduced Th1‐cell differentiation. Thus in contrast to the in vitro findings with F. monophora‐induced human DC and T‐cell priming 14, Mincle suppressed Th17 but not Th1‐cell differentiation in our in vivo model of murine F. pedrosoi infection. To summarize, the most striking observation is that the Dectin‐2/FcRγ/Card9 signaling pathway is required for Th17‐cell differentiation whereas Mincle engagement is suppressing Th17 cell polarization.
Affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.