The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine

Science. 2011 Oct 14;334(6053):255-8. doi: 10.1126/science.1209791.

Abstract

The mammalian intestine is home to ~100 trillion bacteria that perform important metabolic functions for their hosts. The proximity of vast numbers of bacteria to host intestinal tissues raises the question of how symbiotic host-bacterial relationships are maintained without eliciting potentially harmful immune responses. Here, we show that RegIIIγ, a secreted antibacterial lectin, is essential for maintaining a ~50-micrometer zone that physically separates the microbiota from the small intestinal epithelial surface. Loss of host-bacterial segregation in RegIIIγ(-/-) mice was coupled to increased bacterial colonization of the intestinal epithelial surface and enhanced activation of intestinal adaptive immune responses by the microbiota. Together, our findings reveal that RegIIIγ is a fundamental immune mechanism that promotes host-bacterial mutualism by regulating the spatial relationships between microbiota and host.

Publication types

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

MeSH terms

  • Adaptive Immunity
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Load
  • Gram-Negative Bacteria / immunology
  • Gram-Negative Bacteria / physiology*
  • Gram-Positive Bacteria / immunology
  • Gram-Positive Bacteria / physiology*
  • Homeostasis
  • Immunoglobulin A / analysis
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology*
  • Intestine, Small / immunology
  • Intestine, Small / microbiology*
  • Lectins, C-Type / physiology
  • Metagenome*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Pancreatitis-Associated Proteins
  • Proteins / metabolism*
  • Symbiosis
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Anti-Bacterial Agents
  • Immunoglobulin A
  • Lectins, C-Type
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Pancreatitis-Associated Proteins
  • Proteins
  • Reg3g protein, mouse