Exosomes Released from Cells Infected with Crohn's Disease-associated Adherent-Invasive Escherichia coli Activate Host Innate Immune Responses and Enhance Bacterial Intracellular Replication
Exosomes Released from Cells Infected with Crohn's Disease-associated Adherent-Invasive Escherichia coli Activate Host Innate Immune Responses and Enhance Bacterial Intracellular Replication
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DOI：
10.1097/mib.0000000000000635
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发表时间：
2016-03-01
影响因子：
4.9
通讯作者：
Hang Thi Thu Nguyen
中科院分区：
文献类型：
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作者：
Carriere, Jessica;Bretin, Alexis;Hang Thi Thu Nguyen
背景：克罗恩病是一种慢性炎症性肠病，其病因涉及环境、遗传和微生物因素。据报道，在克罗恩病患者的肠粘膜中，粘附侵袭性大肠杆菌（AIEC）的患病率很高。外泌体是细胞外囊泡，其在细胞间通讯中起作用，并参与宿主对细胞内病原体的应答。方法：用AIEC参考株LF 82或非致病性大肠杆菌感染人肠上皮T84细胞、THP-1巨噬细胞和CEABAC 10转基因小鼠。coliK-12 MG 1655菌株。结果：LF 82感染诱导T84和THP-1细胞释放exosomes。与未感染或MG 1655感染的T84细胞释放的外泌体相比，LF 82感染的细胞释放的外泌体激活了核因子-κ B、促分裂原活化蛋白激酶p38和c-Jun N-末端激酶，并增加了初始THP-1巨噬细胞中促炎细胞因子的分泌。THP-1巨噬细胞的LF 82感染还诱导了外泌体的释放，所述外泌体在受体THP-1细胞中引发促炎反应。重要的是，与用未感染细胞分泌的外泌体刺激相比，用从LF 82感染的细胞释放的外泌体刺激T84或THP-1细胞增加了LF 82细胞内复制。从感染LF 82的CEABAC 10转基因小鼠肠腔中纯化的外泌体增加了小鼠RAW 264.7巨噬细胞中的促炎反应，与未感染或MG 1655感染的小鼠相比。结论：外泌体是宿主与AIEC相互作用的新介质，其能够激活先天免疫反应并颠覆AIEC复制的控制。
Background:Crohn's disease is a chronic inflammatory bowel disease, of which the etiology involves environmental, genetic, and microbial factors. A high prevalence of adherent-invasive Escherichia coli, named AIEC, has been reported in the intestinal mucosa of patients with Crohn's disease. Exosomes are extracellular vesicles that function in intercellular communication and have been implicated in host responses to intracellular pathogens. We investigated the potential involvement of exosomes in host response to AIEC infection.Methods:Human intestinal epithelial T84 cells, THP-1 macrophages, and CEABAC10 transgenic mice were infected with the AIEC reference strain LF82 or the nonpathogenic E. coli K-12 MG1655 strain. Exosomes were purified using the ExoQuick reagent.Results:LF82 infection induced the release of exosomes by T84 and THP-1 cells. Compared with exosomes released from the uninfected or MG1655-infected T84 cells, those released from LF82-infected cells activated nuclear factor-kappa B, mitogen-activated protein kinases p38, and c-Jun N-terminal kinase and increased the secretion of proinflammatory cytokines in naive THP-1 macrophages. LF82 infection of THP-1 macrophages also induced the release of exosomes that triggered a proinflammatory response in recipient THP-1 cells. Importantly, stimulation of T84 or THP-1 cells with exosomes released from LF82-infected cells increased LF82 intracellular replication compared with stimulation with exosomes secreted by uninfected cells. Exosomes purified from intestinal lumen of CEABAC10 transgenic mice infected with LF82 increased proinflammatory responses in murine RAW 264.7 macrophages compared with those from uninfected or MG1655-infected mice.Conclusions:Exosomes are new mediators of host-AIEC interaction with their capacity to activate innate immune responses and subvert the control of AIEC replication.