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

• Published in: PLoS pathogens Vol. 15; no. 6; p. e1007866
• Main Authors: Arnold, Isabelle C., Zhang, Xiaozhou, Artola-Boran, Mariela, Fallegger, Angela, Sander, Peter, Johansen, Pål, Müller, Anne
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2019; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Bacillus Calmette-Guerin vaccine; Bacteria; Bacterial infections; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - immunology; BCG; Biology and Life Sciences; Cancer; CD103 antigen; Cell Line, Tumor; Chemokines; Chemokines, CXC - genetics; Chemokines, CXC - immunology; Colon; Colon cancer; Colorectal cancer; CXCR3 protein; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - microbiology; Dendritic Cells - pathology; Dependence; Effector cells; Helicobacter infections; Helicobacter Infections - genetics; Helicobacter Infections - immunology; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - immunology; Immunity; Immunology; Infection; Infection control; Infections; Lamina propria; Lymphocytes; Lymphocytes T; Medical research; Medicine and Health Sciences; Mice; Mice, Knockout; Microbiota; Mycobacterium bovis - immunology; Mycobacterium infections; Myeloid cells; Neuropilin; Polymerase chain reaction; Population; Receptors, CXCR3 - genetics; Receptors, CXCR3 - immunology; Recruitment; Repressor Proteins - genetics; Repressor Proteins - immunology; Research and Analysis Methods; Risk factors; Small intestine; T cell receptors; T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - microbiology; T-Lymphocytes, Regulatory - pathology; Transcription factors; Transplants & implants; Tuberculosis - genetics; Tuberculosis - immunology; Tuberculosis - pathology; Switzerland
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007866

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.