title: C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America.
abstract: Vaccine immunity to the endemic mycoses of North America requires Th17 cells, but the pattern recognition receptors and signaling pathways that drive these protective responses have not been defined. We show that C-type lectin receptors exert divergent contributions to the development of antifungal Th17 cells and vaccine resistance against Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides posadasii. Acquired immunity to B. dermatitidis requires Dectin-2, whereas vaccination against H. capsulatum and C. posadasii infection depends on innate sensing by Dectin-1 and Dectin-2, but not Mincle. Tracking Ag-specific T cells in vivo established that the Card9 signaling pathway acts indispensably and exclusively on differentiation of Th17 cells, while leaving intact their activation, proliferation, survival, and migration. Whereas Card9 signaling is essential, C-type lectin receptors offer distinct and divergent contributions to vaccine immunity against these endemic fungal pathogens. Our work provides new insight into innate immune mechanisms that drive vaccine immunity and Th17 cells.
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI, 53792.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI, 53792.
authors.forename: Vanessa
authors.initials: V
authors.lastname: LeBert
authors.affiliation: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, Texas.
authors.forename: Chiung Yu
authors.initials: CY
authors.lastname: Hung
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI, 53792.
authors.forename: Kevin
authors.initials: K
authors.lastname: Galles
authors.affiliation: Center for Experimental Medicine and Systems Biology, University of Tokyo, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, Texas.
authors.forename: Garry T
authors.initials: GT
authors.lastname: Cole
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI, 53792.|Department of Internal Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI, 53792.|Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI, 53792.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Klein
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI, 53792.
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000276:immunology; D019264:Adoptive Transfer; D000818:Animals; D020296:Animals, Congenic; D000908:Antibodies, Fungal / Q000096:biosynthesis / Q000276:immunology; D001758:Blastomyces / Q000276:immunology*; D001759:Blastomycosis / Q000453:epidemiology / Q000517:prevention & control*; D053468:CARD Signaling Adaptor Proteins; D003045:Coccidioides / Q000276:immunology*; D003047:Coccidioidomycosis / Q000453:epidemiology / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D019353:Endemic Diseases; D005657:Fungal Vaccines / Q000276:immunology*; D006658:Histoplasma / Q000276:immunology*; D006660:Histoplasmosis / Q000453:epidemiology / Q000517:prevention & control*; D037181:Lectins, C-Type / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011828:Radiation Chimera; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D014611:Vaccination; D000099181:Dectin-1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000908:Antibodies, Fungal; D053468:CARD Signaling Adaptor Proteins; D016207:Cytokines; D005657:Fungal Vaccines; D037181:Lectins, C-Type; D008565:Membrane Proteins; D000099181:Dectin-1; C513280:Card9 protein, mouse; C113583:Clecsf8 protein, mouse; C445340:dectin-2, mouse