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

• Main Authors: Patrick A McLaughlin, Julie A Bettke, Jason W Tam, Jesse Leeds, James B Bliska, Brian P Butler, Adrianus W M van der Velden
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2019-07-01
• Series: PLoS Pathogens
• Online Access: https://doi.org/10.1371/journal.ppat.1007847

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.