title: Fonsecaea pedrosoi-induced Th17-cell differentiation in mice is fostered by Dectin-2 and suppressed by Mincle recognition.
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.
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
authors.forename: Mengyi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
authors.forename: Tassanee
authors.initials: T
authors.lastname: Lerksuthirat
authors.affiliation: Department of Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hardison
authors.affiliation: Department of Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.|Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA.|Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Bruce
authors.initials: B
authors.lastname: Klein
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D002862:Chromoblastomycosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007279:Injections, Subcutaneous; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D004718:Saccharomycetales / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction; D012867:Skin / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013172:Spores, Fungal / Q000276:immunology / Q000472:pathogenicity; D000072377:Syk Kinase; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; C113583:Clecsf8 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D017452:Receptors, IgG; C445340:dectin-2, mouse; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse
keywords: C-type lectin; Chromoblastomycosis; Dectin-2; Fungi; Mincle; T-cell differentiation; Th17 cell