Department of Microbiological Surveillance and Research, Statens Serum Institut, Denmark.
J Infect Dis. 2012 Sep 1;206(5):714-22. doi: 10.1093/infdis/jis417. Epub 2012 Jun 21.
Enteroaggregative Escherichia coli (EAEC) are increasingly recognized as an important agent of inflammatory and often persistent diarrhea. Although previous studies report on the inflammatory aspects of EAEC pathogenesis, the mechanisms by which EAEC trigger these events are not well understood.
EAEC strains harboring mutations in known EAEC virulence determinants were tested in an in vitro model of transepithelial migration of polymorphonuclear neutrophils (PMNs) and in human intestinal xenografts in severe-combined immunodeficient (SCID-HU-INT) mice, a novel model for studying EAEC disease in vivo.
Expression of aggregative adherence fimbriae (AAFs), the principal adhesins of EAEC, was required for EAEC-induced PMN transepithelial migration in vitro. Moreover, constructed plasmids encoding AAF gene clusters demonstrated that the AAF adhesins are sufficient for triggering this event in a nonpathogenic E. coli background. Furthermore, with use of the SCID-HU-INT mouse model, severe tissue damage and infiltration of inflammatory cells was observed in the human tissue after EAEC infection. These pathological marks were strongly related to AAF expression, thus clearly confirming our in vitro findings.
The present work establishes EAEC as an important inflammatory pathogen and the AAF adhesins as inducers of potentially detrimental immune responses.
肠聚集性大肠杆菌（EAEC）越来越被认为是一种重要的炎症性和持续性腹泻的病原体。尽管之前的研究报告了 EAEC 发病机制的炎症方面，但 EAEC 触发这些事件的机制尚不清楚。
在体外多形核中性粒细胞（PMN）跨上皮迁移模型和严重联合免疫缺陷（SCID-HU-INT）小鼠的人肠道异种移植中，测试了携带已知 EAEC 毒力决定簇突变的 EAEC 菌株，SCID-HU-INT 小鼠是一种用于研究 EAEC 疾病的新型体内模型。
表达聚集性粘附纤毛（AAFs），即 EAEC 的主要粘附素，是 EAEC 诱导体外 PMN 跨上皮迁移所必需的。此外，编码 AAF 基因簇的构建质粒表明，AAF 粘附素足以在非致病性大肠杆菌背景下引发这种事件。此外，使用 SCID-HU-INT 小鼠模型，在 EAEC 感染后，人组织中观察到严重的组织损伤和炎症细胞浸润。这些病理标记与 AAF 的表达密切相关，因此清楚地证实了我们的体外发现。
本研究确立了 EAEC 是一种重要的炎症性病原体，AAF 粘附素是潜在有害免疫反应的诱导剂。
