title: Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis.
abstract: Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC) we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs) present in the infected oral mucosa. Candida-derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida-specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity.
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Trautwein-Weidner
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: André
authors.initials: A
authors.lastname: Gladiator
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland; Section of Immunology, Institute of Virology, University of Zürich, Zürich, Switzerland.
authors.forename: Florian R
authors.initials: FR
authors.lastname: Kirchner
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland; Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Becattini
authors.affiliation: Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rülicke
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland; Section of Immunology, Institute of Virology, University of Zürich, Zürich, Switzerland.
authors.forename: Salomé
authors.initials: S
authors.lastname: LeibundGut-Landmann
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000946:Antigens, Fungal / Q000276:immunology; D002180:Candidiasis, Oral / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000946:Antigens, Fungal; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell