Microbial sensing by goblet cells controls immune surveillance of luminal antigens in the colon

Mucosal Immunol. 2015 Jan;8(1):198-210. doi: 10.1038/mi.2014.58. Epub 2014 Jul 9.


The delivery of luminal substances across the intestinal epithelium to the immune system is a critical event in immune surveillance, resulting in tolerance to dietary antigens and immunity to pathogens. How this process is regulated is largely unknown. Recently goblet cell-associated antigen passages (GAPs) were identified as a pathway delivering luminal antigens to underlying lamina propria (LP) dendritic cells in the steady state. Here, we demonstrate that goblet cells (GCs) form GAPs in response to acetylcholine (ACh) acting on muscarinic ACh receptor 4. GAP formation in the small intestine was regulated at the level of ACh production, as GCs rapidly formed GAPs in response to ACh analogs. In contrast, colonic GAP formation was regulated at the level of GC responsiveness to ACh. Myd88-dependent microbial sensing by colonic GCs inhibited the ability of colonic GCs to respond to Ach to form GAPs and deliver luminal antigens to colonic LP-antigen-presenting cells (APCs). Disruption of GC microbial sensing in the setting of an intact gut microbiota opened colonic GAPs, and resulted in recruitment of neutrophils and APCs and production of inflammatory cytokines. Thus GC intrinsic sensing of the microbiota has a critical role regulating the exposure of the colonic immune system to luminal substances.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / administration & dosage
  • Animals
  • Antigen Presentation / drug effects
  • Antigens / immunology
  • Antigens / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cells, Cultured
  • Colon / immunology*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Goblet Cells / drug effects
  • Goblet Cells / immunology*
  • Immunologic Surveillance*
  • Intestinal Mucosa / immunology
  • Intestine, Small / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microbiota / immunology
  • Mutation / genetics
  • Receptors, Muscarinic / metabolism
  • Signal Transduction


  • Antigens
  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Cytoskeletal Proteins
  • Receptors, Muscarinic
  • ezrin
  • Acetylcholine