Inflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine

PLoS Pathog. 2019 Jul 15;15(7):e1007847. doi: 10.1371/journal.ppat.1007847. eCollection 2019 Jul.

Abstract

Salmonella exploit host-derived nitrate for growth in the lumen of the inflamed intestine. The generation of host-derived nitrate is dependent on Nos2, which encodes inducible nitric oxide synthase (iNOS), an enzyme that catalyzes nitric oxide (NO) production. However, the cellular sources of iNOS and, therefore, NO-derived nitrate used by Salmonella for growth in the lumen of the inflamed intestine remain unidentified. Here, we show that iNOS-producing inflammatory monocytes infiltrate ceca of mice infected with Salmonella. In addition, we show that inactivation of type-three secretion system (T3SS)-1 and T3SS-2 renders Salmonella unable to induce CC- chemokine receptor-2- and CC-chemokine ligand-2-dependent inflammatory monocyte recruitment. Furthermore, we show that the severity of the pathology of Salmonella- induced colitis as well as the nitrate-dependent growth of Salmonella in the lumen of the inflamed intestine are reduced in mice that lack Ccr2 and, therefore, inflammatory monocytes in the tissues. Thus, inflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine.

Publication types

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

MeSH terms

  • Animals
  • Chemokine CCL2 / deficiency
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Female
  • Host Microbial Interactions / genetics
  • Host Microbial Interactions / physiology
  • Humans
  • Inflammation / metabolism
  • Inflammation / microbiology
  • Inflammation / pathology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Monocytes / metabolism*
  • Monocytes / pathology
  • Nitric Oxide Synthase Type II / metabolism
  • Receptors, CCR2 / deficiency
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism
  • Salmonella Infections, Animal / metabolism
  • Salmonella Infections, Animal / microbiology
  • Salmonella Infections, Animal / pathology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*
  • Salmonella typhimurium / pathogenicity*
  • Type III Secretion Systems / metabolism

Substances

  • Ccl2 protein, mouse
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Receptors, CCR2
  • Type III Secretion Systems
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse