Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM.
Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM.
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DOI：
10.1084/jem.20090741
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发表时间：
2009-09-28
期刊：
影响因子：
--
通讯作者：
Darfeuille-Michaud A
中科院分区：
文献类型：
--
作者：
Carvalho FA;Barnich N;Sivignon A;Darcha C;Chan CH;Stanners CP;Darfeuille-Michaud A
在克罗恩病（CD）患者的回肠上皮的顶端表面观察到CEACAM 6的异常表达，并且CD回肠病变被致病性粘附侵袭性大肠杆菌（AIEC）定殖。我们研究了AIEC参考菌株LF 82在表达人CEACAMs的CEABAC 10转基因小鼠中定殖肠粘膜和诱导炎症的能力。AIEC LF 82强毒菌，而非非致病性E.大肠杆菌K-12，能够持续存在于CEABAC 10转基因小鼠的肠道中，并诱导严重的结肠炎，存活率降低，体重明显减轻，直肠出血增加，存在糜烂性病变，粘膜炎症和促炎细胞因子表达增加。结肠炎依赖于AIEC细菌的1型皮利表达和肠CEACAM表达，因为在感染1型皮利阴性LF 82-ΔfimH同基因突变体的转基因小鼠或感染AIEC LF 82细菌的野生型小鼠中未观察到结肠炎迹象。这些发现强烈支持以下假设：在具有CEACAM 6的异常肠表达的CD患者中，AIEC细菌通过1型皮利表达可以定殖肠粘膜并诱导肠道炎症。因此，靶向AIEC粘附到肠粘膜代表了临床医生预防和/或治疗回肠CD的新策略。
Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). We investigated the ability of AIEC reference strain LF82 to colonize the intestinal mucosa and to induce inflammation in CEABAC10 transgenic mice expressing human CEACAMs. AIEC LF82 virulent bacteria, but not nonpathogenic E. coli K-12, were able to persist in the gut of CEABAC10 transgenic mice and to induce severe colitis with reduced survival rate, marked weight loss, increased rectal bleeding, presence of erosive lesions, mucosal inflammation, and increased proinflammatory cytokine expression. The colitis depended on type 1 pili expression by AIEC bacteria and on intestinal CEACAM expression because no sign of colitis was observed in transgenic mice infected with type 1 pili–negative LF82-ΔfimH isogenic mutant or in wild-type mice infected with AIEC LF82 bacteria. These findings strongly support the hypothesis that in CD patients having an abnormal intestinal expression of CEACAM6, AIEC bacteria via type 1 pili expression can colonize the intestinal mucosa and induce gut inflammation. Thus, targeting AIEC adhesion to gut mucosa represents a new strategy for clinicians to prevent and/or to treat ileal CD.
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影响因子：
4.8
作者：
Claret, Laurent;Miquel, Sylvie;Darfeuille-Michaud, Arlette
通讯作者：
Darfeuille-Michaud, Arlette
影响因子：
9.8
作者：
Neut, C;Bulois, P;Colombel, JF
通讯作者：
Colombel, JF
影响因子：
7.3
作者：
Larsson, A;Johansson, SMC;Linusson, A
通讯作者：
Linusson, A
影响因子：
2.8
作者：
Poggio, Thelma Veronica;La Torre, Jose Leonardo;Scodeller, Eduardo Alberto
通讯作者：
Scodeller, Eduardo Alberto
影响因子：
29.4
作者：
Darfeuille-Michaud, A;Neut, C;Colombel, JF
通讯作者：
Colombel, JF