Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
PLoS One. 2012;7(4):e34812. doi: 10.1371/journal.pone.0034812. Epub 2012 Apr 6.
Enteric pathogens need to grow efficiently in the gut lumen in order to cause disease and ensure transmission. The interior of the gut forms a complex environment comprising the mucosal surface area and the inner gut lumen with epithelial cell debris and food particles. Recruitment of neutrophils to the intestinal lumen is a hallmark of non-typhoidal Salmonella enterica infections in humans. Here, we analyzed the interaction of gut luminal neutrophils with S. enterica serovar Typhimurium (S. Tm) in a mouse colitis model.
Upon S. Tm(wt) infection, neutrophils transmigrate across the mucosa into the intestinal lumen. We detected a majority of pathogens associated with luminal neutrophils 20 hours after infection. Neutrophils are viable and actively engulf S. Tm, as demonstrated by live microscopy. Using S. Tm mutant strains defective in tissue invasion we show that pathogens are mostly taken up in the gut lumen at the epithelial barrier by luminal neutrophils. In these luminal neutrophils, S. Tm induces expression of genes typically required for its intracellular lifestyle such as siderophore production iroBCDE and the Salmonella pathogenicity island 2 encoded type three secretion system (TTSS-2). This shows that S. Tm at least transiently survives and responds to engulfment by gut luminal neutrophils. Gentamicin protection experiments suggest that the life-span of luminal neutrophils is limited and that S. Tm is subsequently released into the gut lumen. This "fast cycling" through the intracellular compartment of gut luminal neutrophils would explain the high fraction of TTSS-2 and iroBCDE expressing intra- and extracellular bacteria in the lumen of the infected gut.
In conclusion, live neutrophils recruited during acute S. Tm colitis engulf pathogens in the gut lumen and may thus actively engage in shaping the environment of pathogens and commensals in the inflamed gut.
肠道病原体需要在肠道腔中高效生长，才能引起疾病并确保传播。肠道内部形成了一个复杂的环境，包括黏膜表面积和含有上皮细胞碎片和食物颗粒的肠道内腔。中性粒细胞向肠道腔的募集是人类非伤寒沙门氏菌感染的非伤寒沙门氏菌感染的标志。在这里，我们在小鼠结肠炎模型中分析了肠道腔中性粒细胞与肠炎沙门氏菌血清型 Typhimurium（S. Tm）的相互作用。
在 S. Tm（wt）感染后，中性粒细胞穿过黏膜进入肠道腔。我们在感染后 20 小时检测到与肠道腔中性粒细胞相关的大多数病原体。活显微镜显示，中性粒细胞是有活力的，并积极吞噬 S. Tm。使用组织侵袭缺陷的 S. Tm 突变株，我们表明病原体主要是由肠道腔中的中性粒细胞在肠上皮屏障处摄取的。在这些肠道腔中性粒细胞中，S. Tm 诱导其细胞内生活方式所需的基因表达，例如铁载体产生iroBCDE 和沙门氏菌致病性岛 2 编码的 III 型分泌系统（TTSS-2）。这表明 S. Tm 至少暂时存活并对肠道腔中性粒细胞的吞噬作用作出反应。庆大霉素保护实验表明，肠道腔中性粒细胞的寿命有限，随后 S. Tm 被释放到肠道腔中。这种通过肠道腔中性粒细胞的细胞内隔室的“快速循环”将解释感染肠道中腔内 TTSS-2 和 iroBCDE 表达的胞内和胞外细菌的高比例。
总之，在急性 S. Tm 结肠炎期间募集的活中性粒细胞吞噬肠道腔中的病原体，因此可能积极参与塑造炎症肠道中病原体和共生体的环境。
