Journal article

Antigen-specific Th17 cells are primed by distinct and complementary dendritic cell subsets in oropharyngeal candidiasis

  • Trautwein-Weidner, Kerstin Institute of Microbiology, ETH Zürich, Zürich, Switzerland
  • Gladiator, André Institute of Microbiology, ETH Zürich, Zürich, Switzerland
  • Kirchner, Florian R. Institute of Microbiology, ETH Zürich, Zürich, Switzerland - Section of Immunology, Institute of Virology, University of Zürich, Zürich, Switzerland
  • Becattini, Simone Institute of Microbiology, ETH Zürich, Zürich, Switzerland - Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Rülicke, Thomas Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Vienna, Austria
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • LeibundGut-Landmann, Salomé Institute of Microbiology, ETH Zürich, Zürich, Switzerland - Section of Immunology, Institute of Virology, University of Zürich, Zürich, Switzerland
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    02.10.2015
Published in:
  • PLoS pathogens. - 2015, vol. 11, no. 10, p. e1005164
English 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.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/319083
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