Department of Molecular Genetics and Microbiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, United States of America.
Department of Pathobiology, School of Veterinary Medicine at Saint George's University, Grenada, West-Indies.
PLoS Pathog. 2019 Jul 15;15(7):e1007847. doi: 10.1371/journal.ppat.1007847. eCollection 2019 Jul.
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.
沙门氏菌利用宿主来源的硝酸盐在发炎肠道的腔道中生长。宿主来源的硝酸盐的产生依赖于 Nos2，它编码诱导型一氧化氮合酶（iNOS），一种催化一氧化氮（NO）产生的酶。然而，iNOS 的细胞来源，以及因此，沙门氏菌用于在发炎肠道腔道中生长的 NO 衍生硝酸盐仍然未被确定。在这里，我们表明，产生 iNOS 的炎症单核细胞浸润感染沙门氏菌的小鼠的盲肠。此外，我们表明，III 型分泌系统（T3SS）-1 和 T3SS-2 的失活使沙门氏菌无法诱导 CC 趋化因子受体-2 和 CC 趋化因子配体-2 依赖性炎症单核细胞募集。此外，我们表明，缺乏 Ccr2 的小鼠中，沙门氏菌诱导的结肠炎的病理学严重程度以及硝酸盐依赖的沙门氏菌在发炎肠道腔道中的生长程度降低，因此，组织中的炎症单核细胞减少。因此，炎症单核细胞为沙门氏菌在发炎肠道的腔道中扩张提供了一个小生境。
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