The lipoprotein HP1454 of Helicobacter pylori regulates T-cell response by shaping T-cell receptor signalling
The lipoprotein HP1454 of Helicobacter pylori regulates T-cell response by shaping T-cell receptor signalling
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DOI：
10.1111/cmi.13006
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发表时间：
2019-05-01
影响因子：
3.4
通讯作者：
D'Elios, Mario M.
中科院分区：
文献类型：
--
作者：
Capitani, Nagaja;Codolo, Gaia;D'Elios, Mario M.
幽门螺杆菌(Hp)是一种革兰氏阴性菌，慢性感染超过50%的人的胃，是胃癌、胃淋巴瘤、胃自身免疫和消化性溃疡的主要原因。幽门螺杆菌的哪些毒力因子在胃病的发生发展中起重要作用仍有待阐明。在这里，我们分析了HP1454蛋白在宿主-病原体相互作用中的作用。我们发现，从慢性胃炎和胃腺癌患者分离的T细胞中，有相当大比例的T细胞对HP1454有反应而增殖。此外，我们在体内证明了HP1454蛋白驱动Th1/Th17炎症反应。我们进一步分析了人T细胞对Hp野生型毒株和hp1454基因缺失毒株的体外反应，发现HP1454触发了T细胞抗原受体依赖的信号传递和淋巴细胞增殖，以及CXCL12依赖的细胞黏附和迁移。我们的研究结果证明，HP1454是一种关键的细菌因子，通过直接调节T细胞反应来发挥其促炎活性。考虑到令人信服的证据表明慢性胃炎--一种为幽门螺杆菌相关疾病铺平道路的疾病--依赖于T细胞，这些结果的相关性可以得到评价。
Helicobacter pylori (HP) is a Gram-negative bacterium that chronically infects the stomach of more than 50% of human population and represents a major cause of gastric cancer, gastric lymphoma, gastric autoimmunity, and peptic ulcer. It still remains to be elucidated, which HP virulence factors are important in the development of gastric disorders. Here, we analysed the role of the HP protein HP1454 in the host-pathogen interaction. We found that a significant proportion of T cells isolated from HP patients with chronic gastritis and gastric adenocarcinoma proliferated in response to HP1454. Moreover, we demonstrated in vivo that HP1454 protein drives Th1/Th17 inflammatory responses. We further analysed the in vitro response of human T cells exposed either to an HP wild-type strain or to a strain with a deletion of the hp1454 gene, and we revealed that HP1454 triggers the T-cell antigen receptor-dependent signalling and lymphocyte proliferation, as well as the CXCL12-dependent cell adhesion and migration. Our study findings prove that HP1454 is a crucial bacterial factor that exerts its proinflammatory activity by directly modulating the T-cell response. The relevance of these results can be appreciated by considering that compelling evidence suggest that chronic gastric inflammation, a condition that paves the way to HP-associated diseases, is dependent on T cells.