Inflammatory 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.沙门氏菌（Salmonella）可利用宿主源性硝酸盐在炎症肠道肠腔内增殖。宿主源性硝酸盐的生成依赖于Nos2基因，该基因编码诱导型一氧化氮合酶（inducible nitric oxide synthase, iNOS）——一种催化一氧化氮（nitric oxide, NO）合成的酶。然而，沙门氏菌在炎症肠道肠腔中增殖所依赖的iNOS细胞来源，以及由此产生的NO衍生硝酸盐的来源，至今仍未明确。本研究证实，产iNOS的炎症单核细胞会浸润沙门氏菌感染小鼠的盲肠组织。此外，研究发现，灭活三型分泌系统（type-three secretion system, T3SS）-1与T3SS-2会使沙门氏菌无法诱导依赖CC趋化因子受体2（CC-chemokine receptor 2, CCR2）与CC趋化因子配体2（CC-chemokine ligand 2, CCL2）的炎症单核细胞招募。进一步研究表明，缺失Ccr2基因（因此其组织内缺乏炎症单核细胞）的小鼠，其沙门氏菌诱导性结肠炎的病理严重程度，以及沙门氏菌在炎症肠道肠腔中的硝酸盐依赖性增殖水平均显著降低。综上，炎症单核细胞为沙门氏菌在炎症肠道肠腔中的扩增提供了专属微环境。