Abnormalities in the Handling of Intracellular Bacteria in Crohn's Disease
Abnormalities in the Handling of Intracellular Bacteria in Crohn's Disease
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DOI：
10.1097/mcg.0b013e3181dd4fa5
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发表时间：
2010-09-01
影响因子：
2.9
通讯作者：
Darfeuille-Michaud, Arlette
中科院分区：
文献类型：
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作者：
Lapaquette, Pierre;Darfeuille-Michaud, Arlette
克罗恩病（CD）患者的回肠病变是由致病性粘附-侵袭性大肠杆菌（AIEC）定植的，这些大肠杆菌能够侵入并在肠上皮细胞内复制。近年来的研究进展强调了先天免疫系统的重要性以及肠道菌群和肠粘膜之间的关键关系。已经描述了几种遗传易感因素的组合，其中最重要的可复制关联包括细菌细胞壁细胞内受体（NOD2/CARD15）的基因，以及通过自噬进行细菌清除和抗原加工的基因（ATG16L1和IRGM）。我们最近报道，在IRGM和ATG16L1缺陷的细胞中，细胞内AIEC LF82细菌的复制能力增强，令人惊讶的是，自噬缺陷并没有干扰任何其他大肠杆菌菌株的细胞内细菌的生存和/或复制能力，包括与胃肠炎有关的非致病性、环境性、共生性或致病性菌株。由于自噬是一种先天防御机制，作为一种细胞自主系统，用于消除细胞内病原体，这些发现使包括AIEC在内的细胞内细菌可能在CD发病机制中发挥作用的概念更加重要。
Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to invade and to replicate within intestinal epithelial cells. Recent advances have highlighted the importance of the innate immune system and the critical relationship between the gut flora and the intestinal mucosa. Several combinations of genetic predisposing factors to CD have been described, with the most significant replicable associations including genes for intracellular receptor of bacterial cell walls (NOD2/CARD15), and for bacterial clearance and antigen processing through autophagy (ATG16L1 and IRGM). We recently reported that in IRGM and ATG16L1 deficient cells, intracellular AIEC LF82 bacteria have enhanced replication and that autophagy deficiency surprisingly did not interfere with the ability of intracellular bacteria to survive and/or replicate for any other E. coli strains tested, including nonpathogenic, environmental, commensal, or pathogenic strains involved in gastroenteritis. As autophagy is an innate defense mechanism acting as a cell-autonomous system for elimination of intracellular pathogens, these findings lead weight to the notion that intracellular bacteria including AIEC might play a role in CD pathogenesis.