Abstract
The gastric lamina propria of mice that have been experimentally infected with the pathobiont Helicobacter pylori hosts a dense network of myeloid cells that includes BATF3-dependent CD103+ dendritic cells (DCs). We show here that CD103+ DCs are strictly required for gastric Th1 responses to H. pylori and for H. pylori infection control. A similar dependence of type 1 immunity on CD103+ DCs is observed in a Mycobacterium bovis BCG infection model, and in a syngeneic colon cancer model. Strikingly, we find that not only the expansion and/or recruitment of Th1 cells, but also of peripherally induced, neuropilin-negative regulatory T-cells to sites of infection requires BATF3-dependent DCs. A shared feature of the examined models is the strongly reduced production of the chemokines and CXCR3 ligands CXCL9, 10 and 11 in BATF3-deficient mice. The results implicate BATF3-dependent DCs in the recruitment of CXCR3+ effector and regulatory T-cells to target tissues and in their local expansion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / immunology*
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Cell Line, Tumor
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Chemokines, CXC / genetics
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Chemokines, CXC / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / microbiology
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Dendritic Cells / pathology
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Helicobacter Infections / genetics
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Helicobacter Infections / immunology*
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Helicobacter Infections / pathology
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Helicobacter pylori / immunology*
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Mice
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Mice, Knockout
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Mycobacterium bovis / immunology*
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Receptors, CXCR3 / genetics
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Receptors, CXCR3 / immunology
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Repressor Proteins / genetics
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Repressor Proteins / immunology*
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / microbiology
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T-Lymphocytes, Regulatory / pathology
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Tuberculosis / genetics
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Tuberculosis / immunology*
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Tuberculosis / pathology
Substances
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Basic-Leucine Zipper Transcription Factors
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Chemokines, CXC
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Cxcr3 protein, mouse
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Receptors, CXCR3
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Repressor Proteins
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SNFT protein, mouse
Grants and funding
This work was supported by the Swiss National Science Foundation (SNF) Temporary Backup Schemes Consolidator Grant BSCGIO_157841/1 to A.M. and the clinical research priority program on Human Hemato-Lymphatic Diseases, University of Zurich, also to A.M. The funding sources had no role in the design or execution of the research.