Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis

PLoS Pathogens

Federica Sallusto¹  Salomé LeibundGut-Landmann²  Kerstin Trautwein-Weidner³  André Gladiator³  Thomas Rülicke³  Florian R. Kirchner³  Simone Becattini⁴ 

[1] Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland;Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Vienna, Austria;Institute of Microbiology, ETH Zürich, Zürich, Switzerland;Section of Immunology, Institute of Virology, University of Zürich, Zürich, Switzerland

关键词: T cells;    Lymph nodes;    C;    ida albicans;    Hybridomas;    Major histocompatibility complex;    Antigen-presenting cells;    Cloning;    Cell differentiation;   

DOI  :  10.1371/journal.ppat.1005164

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY