Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection.
Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection.
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DOI：
10.1371/journal.pone.0015398
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发表时间：
2010-11-09
期刊：
影响因子：
3.7
通讯作者：
Bajaj-Elliott M
中科院分区：
文献类型：
--
作者：
Edwards LA;Nistala K;Mills DC;Stephenson HN;Zilbauer M;Wren BW;Dorrell N;Lindley KJ;Wedderburn LR;Bajaj-Elliott M
空肠弯曲菌是世界范围内细菌性胃肠炎最常见的原因。尽管这种感染带来了重大的健康负担，但对C。空肠介导的疾病发病机制仍不清楚。在这里，我们报告的早期，先天性免疫反应的特点，以C。空肠，使用离体人肠道感染模型。其次，还寻求细菌驱动的树突状细胞活化对T细胞介导的免疫的影响。健康的对照儿童末端回肠或结肠活检组织被C.空肠灌胃8-12小时。细菌定植后进行共聚焦显微镜检查，并通过ELISA测量粘膜先天免疫反应。观察到IFNγ的显著诱导以及IL-22和IL-17 A的适度增加。粘膜IL-12、IL-23、IL-1β和IL-6增加表明细胞因子环境可能调节随后的T细胞介导的免疫。C.空肠驱动的人单核细胞衍生的树突细胞活化之后，利用流式细胞术和ELISA分析T细胞免疫应答。Th-17、Th-1、Th-17/Th-1双阳性细胞及相应细胞因子均显著增加。IFNγ、IL-22和IL-17细胞因子通过调节C.通过标准庆大霉素保护试验测量空肠对肠上皮的粘附和侵袭。先天性和适应性T细胞免疫对C。空肠感染导致IFNγ、IL-22和IL-17 A的释放;表明这种细胞因子三联体在感染的急性期和效应期建立宿主抗微生物免疫中的关键作用。此外，除了它们已知的抗微生物功能之外，IL-17 A和IL-17 F减少了细胞内C.空肠肠上皮细胞，突出了一个新的方面，如何IL-17家族成员可能有助于保护性免疫，对C。空肠。
Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Despite the significant health burden this infection presents, molecular understanding of C. jejuni-mediated disease pathogenesis remains poorly defined. Here, we report the characterisation of the early, innate immune response to C. jejuni using an ex-vivo human gut model of infection. Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated immunity was also sought. Healthy, control paediatric terminal ileum or colonic biopsy tissue was infected with C. jejuni for 8–12 hours. Bacterial colonisation was followed by confocal microscopy and mucosal innate immune responses measured by ELISA. Marked induction of IFNγ with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1β and IL-6 were indicative of a cytokine milieu that may modulate subsequent T-cell mediated immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was followed by analyses of T cell immune responses utilising flow cytometry and ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells and corresponding cytokines was observed. The ability of IFNγ, IL-22 and IL-17 cytokines to exert host defence via modulation of C. jejuni adhesion and invasion to intestinal epithelia was measured by standard gentamicin protection assay. Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFNγ, IL-22 and IL-17A; suggesting a critical role for this cytokine triad in establishing host anti-microbial immunity during the acute and effectors phase of infection. In addition, to their known anti-microbial functions; IL-17A and IL-17F reduced the number of intracellular C. jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family members may contribute to protective immunity against C. jejuni.
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