Helicobacter pylori binds to CD74 on gastric epithelial cells and stimulates interleukin-8 production
Helicobacter pylori binds to CD74 on gastric epithelial cells and stimulates interleukin-8 production
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DOI：
10.1128/iai.73.5.2736-2743.2005
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Reyes, VE
中科院分区：
文献类型：
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作者：
Beswick, EJ;Bland, DA;Reyes, VE
与幽门螺杆菌感染相关的发病机制需要与胃上皮细胞持续接触。虽然一些细胞表面受体已经被认为在黏附中发挥作用，但引起宿主反应的细菌-宿主相互作用还没有很好的定义。本研究探讨了幽门螺杆菌与胃上皮细胞高表达的第二类主要组织相容性复合体(MHC)相关不变量链(II；CD74)之间的相互作用。当干扰素(干扰素)或CD74转基因成纤维细胞上调CD74的表面表达时，细菌结合力增加，而CD74封闭抗体、CD74的酶裂解和CD74包被的细菌则降低细菌结合力。在没有第II类MHC的情况下，幽门螺杆菌还可以直接与亲和纯化的CD74结合。CD74的交联性和CD74的接合被证实可以通过在没有第二类MHC的情况下表达CD74的无关细胞株来刺激IL-8的产生。细胞表达CD74的增加增加了对幽门螺杆菌的反应产生IL-8，而阻断CD74的药物降低了这些反应。幽门螺杆菌与CD74的结合为幽门螺杆菌与胃上皮细胞的最初相互作用提供了一个新的视角，从而导致炎症反应的上调。
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-gamma 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.