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

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.

Salmonella Typhimurium uses anaerobic respiration to overcome propionate-mediated colonization resistance

“…Consequently, innate immune cells release reactive oxygen and nitrogen species that react to generate alternative electron acceptors, including tetrathionate and nitrate (23,31,41). The presence of alternative electron acceptors provides S. Tm with the opportunity to perform anaerobic respiration and outgrow the obligate anaerobic microbiota (22,23,41). Furthermore, the inflamed gut is a unique niche in which S. Tm alters its metabolism and begins to utilize carbon sources that require respiration (28).…”

“…Interestingly, S. Tm can take advantage of the nitrate generated by the host immune response by using it as an alternative electron acceptor to fuel anaerobic respiration (21). By performing anaerobic respiration, S. Tm can outgrow the resident microbiota whose metabolism relies on fermentation (22,23). In .…”

“…Interestingly, S. Tm can take advantage of the nitrate generated by the host immune response by using it as an alternative electron acceptor to fuel anaerobic respiration (21). By performing anaerobic respiration, S. Tm can outgrow the resident microbiota whose metabolism relies on fermentation (22,23). In addition to the energetic benefits of anaerobic respiration compared to fermentation, S. Tm's metabolic adaption in the inflamed gut enables the pathogen to access new nutrient niches and metabolize novel carbon sources (24,25).…”

Monocyte dysregulation: consequences for hepatic infections

“…A recent study shows that these complexes interfere with and promote CCL2/CCR2-dependent recruitment of inflammatory monocytes and tissue damage. Pathology and bacterial growth are abolished in CCR2 -/- mice, suggesting that monocytes might serve as a niche for Salmonella , as observed for Leishmania [ 112 ].…”

Microbiota-Nourishing Immunity: A Guide to Understanding Our Microbial Self

“…In case of severe intestinal inflammation, phagocytes can enter the intestinal lumen and consume oxygen by undergoing a respiratory burst, thereby turning the mucosal surface hypoxic (Campbell et al, 2014;Karhausen et al, 2004). However, the respiratory burst of phagocytes generates hostderived electron acceptors, such as tetrathionate and nitrate, which support growth of Enterobacteriaceae through anaerobic respiration (Kamdar et al, 2016;McLaughlin et al, 2019;Winter et al, 2010). Thus, a dysbiotic expansion of facultative anaerobic Proteobacteria in the large intestine is due to an increased availability of host-derived respiratory electron acceptors.…”