Intestinal CD169(+) Macrophages Initiate Mucosal Inflammation by Secreting CCL8 That Recruits Inflammatory Monocytes

Nat Commun. 2015 Jul 21;6:7802. doi: 10.1038/ncomms8802.

Abstract

Lamina propria (LP) macrophages are constantly exposed to commensal bacteria, and are refractory to those antigens in an interleukin (IL)-10-dependent fashion. However, the mechanisms that discriminate hazardous invasion by bacteria from peaceful co-existence with them remain elusive. Here we show that CD169(+) macrophages reside not at the villus tip, but at the bottom-end of the LP microenvironment. Following mucosal injury, the CD169(+) macrophages recruit inflammatory monocytes by secreting CCL8. Selective depletion of CD169(+) macrophages or administration of neutralizing anti-CCL8 antibody ameliorates the symptoms of experimentally induced colitis in mice. Collectively, we identify an LP-resident macrophage subset that links mucosal damage and inflammatory monocyte recruitment. Our results suggest that CD169(+) macrophage-derived CCL8 serves as an emergency alert for the collapse of barrier defence, and is a promising target for the suppression of mucosal injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL8 / metabolism*
  • Colitis / chemically induced
  • Colitis / immunology*
  • Colon / immunology*
  • Dextran Sulfate
  • Female
  • Immunity, Mucosal
  • Macrophages / metabolism*
  • Mice
  • Monocytes / physiology*
  • Mucous Membrane / immunology
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism

Substances

  • Ccl8 protein, mouse
  • Chemokine CCL8
  • Sialic Acid Binding Ig-like Lectin 1
  • Siglec1 protein, mouse
  • Dextran Sulfate