Bacterial-epithelial contact is a key determinant of host innate immune responses to enteropathogenic and enteroaggregative Escherichia coli.
Bacterial-epithelial contact is a key determinant of host innate immune responses to enteropathogenic and enteroaggregative Escherichia coli.
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细菌-上皮接触是宿主对致病性和肠聚集性大肠杆菌的先天免疫反应的关键决定因素。
DOI：
10.1371/journal.pone.0027030
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Phillips AD
中科院分区：
文献类型：
--
作者：
Edwards LA;Bajaj-Elliott M;Klein NJ;Murch SH;Phillips AD
肠致病性（EPEC）和肠聚集性（EAEC）E.大肠杆菌具有相似但不同的临床症状和发病模式。然而，当它们感染胃肠道时，认为它们的鞭毛蛋白引起IL-8释放，导致中性粒细胞募集和胃肠炎。然而，这可能不是故事的全部，因为细菌粘附对IEC先天性应答的影响仍然不清楚。因此，我们已经确定了哪些细菌基序有助于先天上皮细胞对EPEC和EAEC的反应，使用一系列EPEC和EAEC同基因突变株。将Caco-2和HEp-2细胞系暴露于原型EPEC菌株E2348/69或EAEC菌株O 42以及一系列同基因突变菌株。E69 [LPS，非运动性，非粘附性，3型分泌系统（TTSS）阴性，信号传导阴性]或O 42 [非运动性，非粘附性]。测定IL-8和CCL 20蛋白分泌。通过负染透射电子显微镜评估细菌表面结构。进行粘附肌动蛋白染色试验以确定细菌粘附。以前的研究已经报道了宿主促炎反应和微生物抑制这种反应之间的平衡。在我们的系统中，E69 WT和O 42 WT在更大程度上观察到宿主促炎反应的总体平衡，这与临床症状相符。在去除外部EPEC结构鞭毛、LPS、BFP、EspA和EspC;以及EAEC鞭毛和AAF时，宿主炎症反应降低。然而，E69淋巴抑制素的去除增加了宿主的炎症反应，表明参与了细菌介导的抗炎反应。上皮细胞的反应是由于细菌激动剂的组合，与宿主细菌接触这些先天性反应的关键决定因素。宿主上皮细胞的识别被微生物下调炎症反应的能力所抵消。了解这种宿主-微生物平衡的复杂性将有助于改进传染性胃肠炎的疫苗设计。
Enteropathogenic (EPEC) and Enteroaggregative (EAEC) E. coli have similar, but distinct clinical symptoms and modes of pathogenesis. Nevertheless when they infect the gastrointestinal tract, it is thought that their flagellin causes IL-8 release leading to neutrophil recruitment and gastroenteritis. However, this may not be the whole story as the effect of bacterial adherence to IEC innate response(s) remains unclear. Therefore, we have characterized which bacterial motifs contribute to the innate epithelial response to EPEC and EAEC, using a range of EPEC and EAEC isogenic mutant strains. Caco-2 and HEp-2 cell lines were exposed to prototypical EPEC strain E2348/69 or EAEC strain O42, in addition to a range of isogenic mutant strains. E69 [LPS, non-motile, non-adherent, type three secretion system (TTSS) negative, signalling negative] or O42 [non-motile, non-adherent]. IL-8 and CCL20 protein secretion was measured. Bacterial surface structures were assessed by negative staining Transmission Electron Microscopy. The Fluorescent-actin staining test was carried out to determine bacterial adherence. Previous studies have reported a balance between the host pro-inflammatory response and microbial suppression of this response. In our system an overall balance towards the host pro-inflammatory response is seen with the E69 WT and to a greater extent O42 WT, which is in fit with clinical symptoms. On removal of the external EPEC structures flagella, LPS, BFP, EspA and EspC; and EAEC flagella and AAF, the host inflammatory response is reduced. However, removal of E69 lymphostatin increases the host inflammatory response suggesting involvement in the bacterial mediated anti-inflammatory response. Epithelial responses were due to combinations of bacterial agonists, with host-bacterial contact a key determinant of these innate responses. Host epithelial recognition was offset by the microbe's ability to down-regulate the inflammatory response. Understanding the complexity of this host-microbial balance will contribute to improved vaccine design for infectious gastroenteritis.
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DOI：
10.1128/cdli.11.3.548-551.2004
发表时间：
2004-05-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Huang, DB;DuPont, HL;Okhuysen, PC
通讯作者：
Okhuysen, PC
DOI：
10.1152/ajpgi.1999.277.1.g201
发表时间：
1999-07-01
影响因子：
4.5
作者：
Ismaili, A;Meddings, JB;Sherman, PM
通讯作者：
Sherman, PM
DOI：
10.1038/nri2335
发表时间：
2008-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Chaudhuri RR;Sebaihia M;Hobman JL;Webber MA;Leyton DL;Goldberg MD;Cunningham AF;Scott-Tucker A;Ferguson PR;Thomas CM;Frankel G;Tang CM;Dudley EG;Roberts IS;Rasko DA;Pallen MJ;Parkhill J;Nataro JP;Thomson NR;Henderson IR
通讯作者：
Henderson IR
DOI：
10.1073/pnas.0605200103
发表时间：
2006-08-15
影响因子：
11.1
作者：
Feuillet, Vincent;Medjane, Samir;Alexopoulou, Lena
通讯作者：
Alexopoulou, Lena