biostudies-literatureMcLaughlin PANIAID NIH HHSSaint George's University, School of Veterinary MedicineNational Institutes of Healthe1007847https://www.ebi.ac.uk/biostudies/studies/S-EPMC6658010biostudies-literatureUnknown15(7)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.PLoS pathogensInflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine.PMC6658010AI128372R01 AI101221Postdoctoral Scholars Program Training GrantR21 AI128372R01 AI153280R01 AI099222AI140002AI101221R21 AI140002Bliska JBLeeds JBettke JAMcLaughlin PAButler BPTam JWvan der Velden AWMfalseInflammatory monocytes provide a niche for Salmonella expansion in the lumen of the inflamed intestine.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.2019-01-01T00:00:00Z2019 Jul2024-02-15T05:03:35.173Z2019-08-28T07:01:28ZS-EPMC66580103130646810.1371/journal.ppat.1007847