DOCK2 confers immunity and intestinal colonization resistance to Citrobacter rodentium infection.
DOCK2 confers immunity and intestinal colonization resistance to Citrobacter rodentium infection.
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DOI：
10.1038/srep27814
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发表时间：
2016-06-13
影响因子：
4.6
通讯作者：
Kanneganti TD
中科院分区：
文献类型：
--
作者：
Liu Z;Man SM;Zhu Q;Vogel P;Frase S;Fukui Y;Kanneganti TD
食物中毒是世界上发病率和死亡率的主要原因之一。啮齿类柠檬酸杆菌是一种肠道病原菌，其自身附着于肠上皮细胞并诱导附着和消退（A/E）病变。细菌引起感染的能力需要宿主肌动蛋白细胞骨架的破坏。Rac依赖的肌动蛋白聚合被称为胞质分裂奉献因子2（DOCK 2）的鸟嘌呤核苷酸交换因子激活。然而，DOCK 2在感染性疾病中的作用在很大程度上未被探索。在这里，我们发现缺乏DOCK 2的小鼠对C.啮齿类感染这些小鼠的C水平升高。啮齿类细菌，表现出更明显的体重减轻和炎症相关的病理，并倾向于细菌传播到全身器官相比，野生型小鼠。我们发现缺乏DOCK 2的小鼠更容易受到C。啮齿动物附着于肠上皮细胞。因此，我们的研究结果强调了DOCK 2在胃肠道免疫中的重要作用。啮齿类感染
Food poisoning is one of the leading causes of morbidity and mortality in the world. Citrobacter rodentium is an enteric pathogen which attaches itself to enterocytes and induces attachment and effacing (A/E) lesions. The ability of the bacterium to cause infection requires subversion of the host actin cytoskeleton. Rac-dependent actin polymerization is activated by a guanine nucleotide exchange factor known as Dedicator of cytokinesis 2 (DOCK2). However, the role of DOCK2 in infectious disease is largely unexplored. Here, we found that mice lacking DOCK2 were susceptible to C. rodentium infection. These mice harbored increased levels of C. rodentium bacteria, showed more pronounced weight loss and inflammation-associated pathology, and were prone to bacterial dissemination to the systemic organs compared with wild-type mice. We found that mice lacking DOCK2 were more susceptible to C. rodentium attachment to intestinal epithelial cells. Therefore, our results underscored an important role of DOCK2 for gastrointestinal immunity to C. rodentium infection.