Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection
Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection
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DOI：
10.1073/pnas.1104598108
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发表时间：
2011-12-06
影响因子：
11.1
通讯作者：
Ottemann, Karen M.
中科院分区：
文献类型：
--
作者：
Rolig, Annah S.;Carter, J. Elliot;Ottemann, Karen M.
宿主对慢性细菌感染的炎症反应通常决定疾病的结果。在胃病原体幽门螺杆菌的情况下，宿主炎症反应导致的结果范围从中度和无症状到更严重的伴随溃疡或癌症。最近发现H.缺乏定向运动但定殖至接近野生型水平的幽门螺杆菌趋化性突变体（Che（-））触发较少的宿主炎症。我们使用这些突变体来观察导致疾病状态减少的宿主免疫反应。在这里，我们报告说，这些突变体是有缺陷的早期胃募集的CD 4（+）T细胞相比，野生型感染。此外，Che（-）突变体感染缺乏免疫应答的T辅助细胞17型（Th 17）组分，如通过细胞内细胞因子染色和免疫荧光通过胃组织中的细胞因子mRNA水平所测量的。我们还发现，Che（-）突变体感染导致的宿主细胞凋亡显著少于野生型感染，这与先前的观察结果一致，即啮齿柠檬酸杆菌感染中的T辅助细胞17型反应是由伴随的细菌和凋亡细胞信号驱动的。我们认为细菌的趋化性使H。幽门螺杆菌进入特定的宿主生态位，允许细菌表达或递送促凋亡宿主细胞因子。这份报告表明，趋化性起着促进细胞凋亡的作用，这表明细菌趋化系统可能作为感染的治疗目标，其症状来自宿主细胞凋亡和组织损伤。
The host inflammatory response to chronic bacterial infections often dictates the disease outcome. In the case of the gastric pathogen Helicobacter pylori, host inflammatory responses result in outcomes that range from moderate and asymptomatic to more severe with concomitant ulcer or cancers. It was found recently that H. pylori chemotaxis mutants (Che(-)), which lack directed motility but colonize to nearly wild-type levels, trigger less host inflammation. We used these mutants to observe host immune responses that resulted in reduced disease states. Here we report that these mutants are defective for early gastric recruitment of CD4(+) T cells compared with wild-type infection. Furthermore, Che(-) mutant infections lack the T-helper cell, type 17 (Th17) component of the immune response, as measured by cytokine mRNA levels in gastric tissue via intracellular cytokine staining and immunofluorescence. We additionally find that a Che(-) mutant infection results in significantly less host cell apoptosis than does wild-type infection, in accordance with previous observations that T-helper cell, type 17 responses in Citrobacter rodentium infections are driven by concomitant bacterial and apoptotic cell signals. We propose that bacterial chemotaxis allows H. pylori to access a particular host niche that allows the bacteria to express or deliver proapoptotic host cell factors. This report indicates that chemotaxis plays a role in enhancing apoptosis, suggesting bacterial chemotaxis systems might serve as therapeutic targets for infections whose symptoms arise from host cell apoptosis and tissue damage.