Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Infect Immun. 2012 Dec;80(12):4089-98. doi: 10.1128/IAI.00161-12. Epub 2012 Sep 10.
Campylobacter jejuni is the most prevalent cause of food-borne gastroenteritis in the developed world; however, the molecular basis of pathogenesis is unclear. Secretion of virulence factors is a key mechanism by which enteric bacterial pathogens interact with host cells to enhance survival and/or damage the host. However, C. jejuni lacks the virulence-associated secretion systems possessed by other enteric pathogens. Many bacterial pathogens utilize outer membrane vesicles (OMVs) for delivery of virulence factors into host cells. In the absence of prototypical virulence-associated secretion systems, OMVs could be an important alternative for the coordinated delivery of C. jejuni proteins into host cells. Proteomic analysis of C. jejuni 11168H OMVs identified 151 proteins, including periplasmic and outer membrane-associated proteins, but also many determinants known to be important in survival and pathogenesis, including the cytolethal distending toxin (CDT). C. jejuni OMVs contained 16 N-linked glycoproteins, indicating a delivery mechanism by which these periplasm-located yet immunogenic glycoproteins can interact with host cells. C. jejuni OMVs possess cytotoxic activity and induce a host immune response from T84 intestinal epithelial cells (IECs), which was not reduced by OMV pretreatment with proteinase K or polymyxin B prior to coincubation with IECs. Pretreatment of IECs with methyl-beta-cyclodextrin partially blocks OMV-induced host immune responses, indicating a role for lipid rafts in host cell plasma membranes during interactions with C. jejuni OMVs. OMVs isolated from a C. jejuni 11168H cdtA mutant induced interleukin-8 (IL-8) to the same extent as did wild-type OMVs, suggesting OMV induction of IL-8 is independent of CDT.
空肠弯曲菌是发达国家最常见的食源性肠胃炎致病菌；然而，其发病机制的分子基础尚不清楚。毒力因子的分泌是肠道细菌病原体与宿主细胞相互作用以增强存活和/或损害宿主的关键机制。然而，空肠弯曲菌缺乏其他肠道病原体所具有的与毒力相关的分泌系统。许多细菌病原体利用外膜囊泡（OMVs）将毒力因子递送至宿主细胞。在缺乏典型的与毒力相关的分泌系统的情况下，OMVs 可能是将空肠弯曲菌蛋白协调递送至宿主细胞的重要替代方式。空肠弯曲菌 11168H OMVs 的蛋白质组分析鉴定出 151 种蛋白质，包括周质和外膜相关蛋白，但也包括许多已知对存活和发病机制很重要的决定因素，包括细胞毒素扩张毒素（CDT）。空肠弯曲菌 OMVs 含有 16 种 N 连接糖蛋白，表明这些位于周质但具有免疫原性的糖蛋白可以通过一种递呈机制与宿主细胞相互作用。空肠弯曲菌 OMVs 具有细胞毒性，并诱导 T84 肠上皮细胞（IECs）产生宿主免疫反应，而用蛋白酶 K 或多粘菌素 B 预先处理 OMVs 并不能降低其与 IECs 共孵育时的活性。用甲基-β-环糊精预处理 IECs 可部分阻断 OMV 诱导的宿主免疫反应，表明在与空肠弯曲菌 OMVs 相互作用过程中，宿主细胞膜的脂筏发挥作用。来自空肠弯曲菌 11168H cdtA 突变株的 OMVs 诱导白介素-8（IL-8）的程度与野生型 OMVs 相同，表明 OMV 诱导 IL-8 的产生不依赖于 CDT。
