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Helicobacter pylori Binds to CD74 on Gastric Epithelial Cells and Stimulates Interleukin-8 Production

机译:幽门螺杆菌与胃上皮细胞的CD74结合并刺激白介素8的产生。

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The pathogenesis associated with Helicobacter pylori infection requires consistent contact with the gastric epithelium. Although several cell surface receptors have been suggested to play a role in adhesion, the bacterium-host interactions that elicit host responses are not well defined. This study investigated the interaction of H. pylori with the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells. Bacterial binding was increased when CD74 surface expression was increased by gamma interferon (IFN-γ) treatment or by fibroblast cells transfected with CD74, while binding was decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated bacteria. H. pylori was also shown to bind directly to affinity-purified CD74 in the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74 were verified to stimulate IL-8 production by unrelated cell lines expressing CD74 in the absence of class II MHC. Increased CD74 expression by cells increased IL-8 production in response to H. pylori, and agents that block CD74 decreased these responses. The binding of H. pylori to CD74 presents a novel insight into an initial interaction of H. pylori with the gastric epithelium that leads to upregulation of inflammatory responses.
机译:幽门螺杆菌感染相关的发病机制需要与胃上皮持续接触。尽管已经提出了几种细胞表面受体在黏附中起作用,但是引起宿主反应的细菌-宿主相互作用还没有很好的定义。这项研究调查了 H的相互作用。幽门螺杆菌具有II类主要组织相容性复合体(MHC)相关的恒定链(Ii; CD74),已被胃上皮细胞高度表达。当通过γ干扰素(IFN-γ)处理或被CD74转染的成纤维细胞增加CD74表面表达时,细菌结合增加,而通过CD74阻断抗体,CD74的酶切和包被CD74的细菌减少结合。 H。幽门螺杆菌还显示在不存在II类MHC的情况下直接结合亲和纯化的CD74。在不存在II类MHC的情况下,证实了CD74的交联和CD74的参与可刺激表达CD74的无关细胞系刺激IL-8的产生。细胞增加的CD74表达增加了响应H的IL-8的产生。幽门螺杆菌和阻断CD74的药物可降低这些反应。 H的绑定。 CD74的幽门螺杆菌 H的初始相互作用提供了新颖的见解。胃上皮引起的幽门螺杆菌引起炎症反应上调。

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