Salmonella transiently reside in luminal neutrophils in the inflamed gut.
Salmonella transiently reside in luminal neutrophils in the inflamed gut.
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DOI：
10.1371/journal.pone.0034812
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stecher B
中科院分区：
文献类型：
--
作者：
Loetscher Y;Wieser A;Lengefeld J;Kaiser P;Schubert S;Heikenwalder M;Hardt WD;Stecher B
肠道病原体需要在肠腔中有效生长，以引起疾病并确保传播。肠道内部形成复杂的环境，包括粘膜表面区域和具有上皮细胞碎片和食物颗粒的内肠腔。中性粒细胞向肠腔的募集是人类非伤寒性肠道沙门氏菌感染的标志。在这里，我们分析了肠腔中性粒细胞与S。鼠伤寒沙门氏菌（S. Tm）在小鼠结肠炎模型中的表达。在S. Tmwt感染时，中性粒细胞穿过粘膜进入肠腔。我们检测到大多数病原体与管腔中性粒细胞感染后20小时。中性粒细胞是有活力的，并积极吞噬S。Tm，如通过活体显微镜所示。利用S. Tm突变株在组织入侵缺陷，我们表明，病原体大多采取了在肠腔中的上皮屏障管腔中性粒细胞。在这些管腔中性粒细胞中，S. Tm诱导其细胞内生活方式通常所需的基因的表达，例如铁载体产生iroBCDE和沙门氏菌致病岛2编码的三型分泌系统（TTSS-2）。这表明S. Tm至少短暂存活并对肠腔中性粒细胞的吞噬作出反应。庆大霉素保护实验表明，管腔中性粒细胞的寿命是有限的，S。Tm随后释放到肠腔中。通过肠腔中性粒细胞的细胞内区室的这种“快速循环”将解释在感染的肠腔中表达细胞内和细胞外细菌的TTSS-2和iroBCDE的高分数。总之，急性S。Tm结肠炎吞噬肠腔中的病原体，因此可能积极参与塑造发炎肠道中的病原体和寄生虫的环境。
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. Tmwt 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.
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影响因子：
5.6
作者：
MCGOVERN, VJ;SLAVUTIN, LJ
通讯作者：
SLAVUTIN, LJ
影响因子：
30.3
作者：
Lupp, Claudia;Robertson, Marilyn L.;Finlay, B. Brett
通讯作者：
Finlay, B. Brett
影响因子：
3.1
作者：
Barthel, M;Hapfelmeier, S;Hardt, WD
通讯作者：
Hardt, WD
影响因子：
3.1
作者：
Rollenhagen, C;Bumann, D
通讯作者：
Bumann, D
DOI：
10.1097/00005176-199301000-00006
发表时间：
1993-01-01
影响因子：
2.9
作者：
SACHDEV, HPS;CHADHA, V;PURI, RK
通讯作者：
PURI, RK