Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T Cell Responses

Immunity. 2018 Jul 17;49(1):151-163.e5. doi: 10.1016/j.immuni.2018.05.009. Epub 2018 Jul 3.


The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX3CR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. We identified that disruption of the microbiota resulted in CX3CR1+ APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to the epithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.

Keywords: AIEC E. coli; IL-10; Salmonella; Th1; intestinal immunity; microbiota; mononuclear phagocytes; oral tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Bacterial Adhesion / immunology
  • CX3C Chemokine Receptor 1 / metabolism*
  • Disease Models, Animal
  • Female
  • Gastrointestinal Microbiome / immunology*
  • Homeostasis
  • Immune Tolerance
  • Immunity, Mucosal
  • Inflammation / immunology
  • Inflammatory Bowel Diseases / immunology
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Male
  • Mice
  • Mononuclear Phagocyte System / immunology*
  • RAW 264.7 Cells
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology*


  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • IL10 protein, mouse
  • Interleukin-10