Intestinal macrophages arising from CCR2(+) monocytes control pathogen infection by activating innate lymphoid cells

Nat Commun. 2015 Aug 13;6:8010. doi: 10.1038/ncomms9010.

Abstract

Monocytes play a crucial role in antimicrobial host defence, but the mechanisms by which they protect the host during intestinal infection remains poorly understood. Here we show that depletion of CCR2(+) monocytes results in impaired clearance of the intestinal pathogen Citrobacter rodentium. After infection, the de novo recruited CCR2(+) monocytes give rise to CD11c(+)CD11b(+)F4/80(+)CD103(-) intestinal macrophages (MPs) within the lamina propria. Unlike resident intestinal MPs, de novo differentiated MPs are phenotypically pro-inflammatory and produce robust amounts of IL-1β (interleukin-1β) through the non-canonical caspase-11 inflammasome. Intestinal MPs from infected mice elicit the activation of RORγt(+) group 3 innate lymphoid cells (ILC3) in an IL-1β-dependent manner. Deletion of IL-1β in blood monocytes blunts the production of IL-22 by ILC3 and increases the susceptibility to infection. Collectively, these studies highlight a critical role of de novo differentiated monocyte-derived intestinal MPs in ILC3-mediated host defence against intestinal infection.

Publication types

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

MeSH terms

  • Animals
  • Citrobacter rodentium / physiology*
  • Enterobacteriaceae Infections / immunology
  • Enterobacteriaceae Infections / microbiology*
  • Immunity, Cellular
  • Immunity, Innate
  • Lymphocytes / physiology*
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred Strains
  • Monocytes / classification*
  • Monocytes / metabolism
  • Receptors, CCR2*

Substances

  • Ccr2 protein, mouse
  • Receptors, CCR2