title: The C-Type Lectin Receptor MCL Mediates Vaccine-Induced Immunity against Infection with Blastomyces dermatitidis.
abstract: C-type lectin receptors (CLRs) are essential in shaping the immune response to fungal pathogens. Vaccine-induced resistance requires Dectin-2 to promote differentiation of antifungal Th1 and Th17 cells. Since Dectin-2 and MCL heterodimerize and both CLRs use FcRγ as the signaling adaptor, we investigated the role of MCL in vaccine immunity to the fungal pathogen Blastomyces dermatitidis. MCL(-/-) mice showed impaired vaccine resistance against B. dermatitidis infection compared to that of wild-type animals. The lack of resistance correlated with the reduced recruitment of Th17 cells to the lung upon recall following experimental challenge and impaired interleukin-17 (IL-17) production by vaccine antigen-stimulated splenocytes in vitro. Soluble MCL fusion protein recognized and bound a water-soluble ligand from the cell wall of vaccine yeast, but the addition of soluble Dectin-2 fusion protein did not augment ligand recognition by MCL. Taken together, our data indicate that MCL regulates the development of vaccine-induced Th17 cells and protective immunity against lethal experimental infection with B. dermatitidis.
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, 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, Madison, Wisconsin, 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, Madison, Wisconsin, USA.
authors.forename: Tassanee
authors.initials: T
authors.lastname: Lerksuthirat
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA Department of Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Klein
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA mwuethri@wisc.edu.
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
mesh_terms: D000818:Animals; D001758:Blastomyces / Q000235:genetics / Q000276:immunology*; D001759:Blastomycosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology
chemical_list: C584161:Clec4d protein, mouse; D005657:Fungal Vaccines; D020381:Interleukin-17; D037181:Lectins, C-Type; D011971:Receptors, Immunologic