BATF3-dependent dendritic cells drive both effector and regulatory T-cell responses in bacterially infected tissues

PLoS Pathog. 2019 Jun 12;15(6):e1007866. doi: 10.1371/journal.ppat.1007866. eCollection 2019 Jun.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / immunology*
  • Cell Line, Tumor
  • Chemokines, CXC / genetics
  • Chemokines, CXC / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Dendritic Cells / pathology
  • Helicobacter Infections / genetics
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / pathology
  • Helicobacter pylori / immunology*
  • Mice
  • Mice, Knockout
  • Mycobacterium bovis / immunology*
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / microbiology
  • T-Lymphocytes, Regulatory / pathology
  • Tuberculosis / genetics
  • Tuberculosis / immunology*
  • Tuberculosis / pathology

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Chemokines, CXC
  • Cxcr3 protein, mouse
  • Receptors, CXCR3
  • Repressor Proteins
  • SNFT protein, mouse

Grant support

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.