Escherichia coli isolates from inflammatory bowel diseases patients survive in macrophages and activate NLRP3 inflammasome.
Escherichia coli isolates from inflammatory bowel diseases patients survive in macrophages and activate NLRP3 inflammasome.
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DOI：
10.1016/j.ijmm.2014.01.002
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Hermoso MA
中科院分区：
文献类型：
--
作者：
De la Fuente M;Franchi L;Araya D;Díaz-Jiménez D;Olivares M;Álvarez-Lobos M;Golenbock D;González MJ;López-Kostner F;Quera R;Núñez G;Vidal R;Hermoso MA
克罗恩病（CD）是一种多因素病理学，与粘附侵袭性大肠杆菌（AIEC）和NLRP 3多态性变体的存在相关。胞内E.大肠杆菌在其他肠道病变（OIP）中的作用以及NLRP 3-炎性体在由这些细菌激活的免疫应答中的作用尚未研究。在这项研究中，我们试图表征从CD，溃疡性结肠炎（UC）和OIP患者中分离的细胞内菌株，并分析NLRP 3-炎性小体在暴露于侵袭性细菌的巨噬细胞中诱导的免疫应答和杀菌活性中的作用。为此，细胞内E.大肠杆菌分离回肠活检，使用庆大霉素保护试验，揭示了流行和CFU/活检的大肠杆菌。CD、UC和OIP患者活检组织中的大肠杆菌含量高于对照组。为了表征细菌分离株，分析了脉冲场凝胶电泳（PFGE）图谱、毒力基因、血清群和系统发育群。我们发现，从特定患者中分离出的细菌密切相关，并共享毒力因子;然而，来自不同患者的菌株具有遗传异质性。在上皮细胞和巨噬细胞中分别评估了分离菌株的AIEC特征，如侵袭性和复制性。来自CD和UC的一些菌株表现出AIEC特性，而来自OIP的菌株则没有。此外，在巨噬细胞中确定了NLRP 3在促炎细胞因子产生和细菌消除中的作用。E.大肠杆菌菌株通过NLRP 3依赖的机制诱导IL-1β;然而，它们被巨噬细胞消除不依赖于NLRP 3。胞内E.大肠杆菌菌株进入肠粘膜和IL-1β的产生可能参与CD和UC的发病。
Crohn’s disease (CD) is a multifactorial pathology associated with the presence of adherent-invasive Escherichia coli (AIEC) and NLRP3 polymorphic variants. The presence of intracellular E. coli in other intestinal pathologies (OIP) and the role of NLRP3-inflammasome in the immune response activated by these bacteria have not been investigated. In this study, we sought to characterize intracellular strains isolated from patients with CD, ulcerative colitis (UC) and OIP, and analyze NLRP3-inflammasome role in the immune response and bactericidal activity induced in macrophages exposed to invasive bacteria. For this, intracellular E. coli isolation from ileal biopsies, using gentamicin-protection assay, revealed a prevalence and CFU/biopsy of E. coli higher in biopsies from CD, UC and OIP patients than in controls. To characterization of bacterial isolates, pulsed-field gel electrophoresis (PFGE) patterns, virulence genes, serogroup and phylogenetic group were analyzed. We found out that bacteria isolated from a given patient were closely related and shared virulence factors; however, strains from different patients were genetically heterogeneous. AIEC characteristics in isolated strains, such as invasive and replicative properties, were assessed in epithelial cells and macrophages, respectively. Some strains from CD and UC demonstrated AIEC properties, but not strains from OIP. Furthermore, the role of NLRP3 in pro-inflammatory cytokines production and bacterial elimination was determined in macrophages. E. coli strains induced IL-1β through NLRP3-dependent mechanism; however, their elimination by macrophages was independent of NLRP3. Invasiveness of intracellular E. coli strains into the intestinal mucosa and IL-1β production may contribute to CD and UC pathogenesis.
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影响因子：
29.7
作者：
Kaser A;Zeissig S;Blumberg RS
通讯作者：
Blumberg RS
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.1
作者：
Del Canto, Felipe;Botkin, Douglas J.;Vidal, Roberto
通讯作者：
Vidal, Roberto
影响因子：
6.4
作者：
Johnson, JR;Stell, AL
通讯作者：
Stell, AL
DOI：
10.1084/jem.20090741
发表时间：
2009-09-28
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carvalho FA;Barnich N;Sivignon A;Darcha C;Chan CH;Stanners CP;Darfeuille-Michaud A
通讯作者：
Darfeuille-Michaud A