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: Innate recognition of F. pedrosoi and F. monophora requires Mincle on murine macrophages and human dendritic cells 8, 14. Since F. pedrosoi spores triggered an adaptive T‐cell response in vivo, we sought to investigate whether surface expressed CLRs are involved in the innate recognition of the fungal spores. We cocultured live F. pedrosoi spores with CLR transformed B3Z T‐cell hybridoma cells expressing an NFAT‐lacZ β‐galatosidase reporter of ITAM signaling 15. In response to spore stimulation, lacZ activity was increased in reporter cells expressing Dectin‐1 and Dectin‐2 and to a lesser extent MCL (Dectin‐3, Clecsf8, or Clec4d) and Mincle, but not in cells expressing FcRγ only (Fig. 2). Since MCL has been shown to hetero‐dimerize with Dectin‐2 16 and induce coexpression of Mincle on the cell surface 17 we also measured lacZ activity in reporter cells coexpressing MCL/Dectin‐2 and MCL/Mincle. Dectin‐2/MCL and Mincle/MCL coexpressing T‐hybridoma cells produced lacZ activity comparable to Dectin‐2 and Mincle single expression cells, respectively, indicating that coexpression of MCL did not increase Dectin‐2 and Mincle induced signaling. Thus, spores recognized by Dectin‐1 and Dectin‐2 induced the strongest signaling activity, whereas Mincle and MCL recognition induced only a weak response.
Affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.