Potentiation of epithelial innate host responses by intercellular communication.
Potentiation of epithelial innate host responses by intercellular communication.
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DOI：
10.1371/journal.ppat.1001194
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发表时间：
2010-11-18
期刊：
影响因子：
6.7
通讯作者：
Hornef MW
中科院分区：
文献类型：
--
作者：
Dolowschiak T;Chassin C;Ben Mkaddem S;Fuchs TM;Weiss S;Vandewalle A;Hornef MW
上皮在感染时有效地吸引免疫细胞，尽管每个细胞的病原微生物数量少且分泌的趋化因子水平中等。在这里，我们研究了细胞之间的水平细胞间通讯是否可能有助于上皮细胞的协调反应。进行单核细胞增生李斯特菌感染、转染和显微注射极化肠上皮细胞层内的单个细胞，并通过荧光显微镜和流式细胞术在单细胞水平上测定活化。令人惊讶的是，L.单核细胞增多症感染主要在未感染的上皮细胞中观察到，尽管存在侵袭依赖性细胞活化。而水平通信是独立的间隙连接形成，细胞因子分泌，离子通量，或一氧化氮合成，NADPH氧化酶（Nox）4依赖性氧自由基的形成是必需的，足以诱导间接上皮细胞活化。这是第一份报告，以描述上皮细胞间的通讯，在先天免疫激活。在微生物感染的非常早期阶段，上皮通讯促进了协调的感染宿主防御。所有体表都覆盖着一层上皮细胞。上皮细胞形成物理屏障，将下面的无菌组织与环境分开。此外，上皮细胞主动感知细菌和病毒感染。病原微生物的识别导致细胞刺激和可溶性介质的分泌，其将专职免疫细胞吸引到感染部位。这种第一线宿主防御非常有效地起作用，尽管病原体的数量通常很少，并且每个上皮细胞分泌的介质的量有限。因此，我们研究了一个单独的上皮细胞的感染是否会导致在汇合的上皮单层内的其他未感染的细胞的激活，从而导致更实质性的宿主应答。事实上，使用肠道病原体单核细胞增生李斯特菌的模型并在单细胞水平上监测感染和上皮活化，我们可以清楚地表明上皮反应主要由未感染的细胞介导。此外，我们确定氧自由基作为潜在的介质，以促进免疫刺激后的水平上皮通信。因此，我们的研究结果提供了一个新的概念，协调上皮宿主微生物感染后，促进水平上皮通信。
The epithelium efficiently attracts immune cells upon infection despite the low number of pathogenic microbes and moderate levels of secreted chemokines per cell. Here we examined whether horizontal intercellular communication between cells may contribute to a coordinated response of the epithelium. Listeria monocytogenes infection, transfection, and microinjection of individual cells within a polarized intestinal epithelial cell layer were performed and activation was determined at the single cell level by fluorescence microscopy and flow cytometry. Surprisingly, chemokine production after L. monocytogenes infection was primarily observed in non-infected epithelial cells despite invasion-dependent cell activation. Whereas horizontal communication was independent of gap junction formation, cytokine secretion, ion fluxes, or nitric oxide synthesis, NADPH oxidase (Nox) 4-dependent oxygen radical formation was required and sufficient to induce indirect epithelial cell activation. This is the first report to describe epithelial cell-cell communication in response to innate immune activation. Epithelial communication facilitates a coordinated infectious host defence at the very early stage of microbial infection. All body surfaces are covered by a single layer of epithelial cells. Epithelial cells form a physical barrier to separate the underlying sterile tissue from the environment. In addition, epithelial cells actively sense bacterial and viral infection. The recognition of pathogenic microorganisms results in cell stimulation and the secretion of soluble mediators that attract professional immune cells to the site of infection. This first line host defence works very efficiently despite the often low number of pathogens and the limited amount of mediators secreted per epithelial cell. We therefore investigated whether infection of one individual epithelial cell would result in activation of other, non-infected cells within a confluent epithelial monolayer resulting in a more substantial host response. Indeed, using the model of the gut pathogen Listeria monocytogenes and monitoring infection and epithelial activation at a single cell level, we can clearly show that the epithelial response is mainly mediated by non-infected cells. Also, we identify oxygen radicals as potential mediators to facilitate horizontal epithelial communication upon immune stimulation. Our results thus provide a novel concept of a coordinated epithelial host response upon microbial infection facilitated by horizontal epithelial communication.
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影响因子：
15.9
作者：
Andonegui, G;Bonder, CS;Kubes, P
通讯作者：
Kubes, P
影响因子：
4
作者：
Lipinski, Simone;Till, Andreas;Rosenstiel, Philip
通讯作者：
Rosenstiel, Philip
DOI：
10.1007/pl00008649
发表时间：
2000-01-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
Köhler, R;Bubert, A;Bubert, B
通讯作者：
Bubert, B
影响因子：
3.9
作者：
Ammendola, R;Ruocchio, MR;Cimino, F
通讯作者：
Cimino, F
影响因子：
56.9
作者：
Dostert, Catherine;Petrilli, Virginie;Tschopp, Jurg
通讯作者：
Tschopp, Jurg