幽门螺杆菌感染的免疫应答及免疫逃逸机制研究进展

Research Advances in Mechanisms of Immune Response and Immune Escape in Helicobacter pylori Infection

摘要

幽门螺杆菌(Helicobacter pylori)是定植在人体胃黏膜的革兰氏阴性微需氧杆菌, 与慢性胃炎、消化性溃疡、胃黏膜相关淋巴组织淋巴瘤、胃肿瘤、胃息肉的发生发展明显相关。H. pylori侵入胃黏膜细胞会激活核因子κB信号通路, 诱导白介素(interleukin, IL)-8释放, 招募抗原提呈细胞(antigen-presenting cell, APC), 刺激宿主产生固有免疫及适应性免疫反应, 使其发挥抗H. pylori的作用。然而, H. pylori具有操纵和破坏宿主免疫系统的能力, 其不仅可通过修饰自身结构, 规避宿主免疫系统识别, 也能够抑制T、B淋巴细胞的增殖和成熟, 促进T细胞凋亡, 影响Th17/Treg的分化平衡, 诱导自身免疫耐受形成。此外, H. pylori还可通过摄取胆固醇, 破坏胃黏膜上皮细胞富含胆固醇的微域, 阻断γ干扰素(interferon-γ, IFN-γ)、IL-22及IL-6受体的组装, 抑制Th1细胞介导的免疫反应, 促进免疫逃逸。因此, 总结H. pylori感染后宿主所产生的免疫反应以及H. pylori规避免疫系统清除的具体机制, 可为H. pylori的临床防治提供参考。

Abstract

Helicobacter pylori is a Gram-negative, microaerobic bacterium that colonizes the human gastric mucosa and is significantly associated with the development of chronic gastritis, peptic ulcer, gastric mu-cosa-associated lymphoma, gastric tumors, and gastric polyps. Infection of gastric mucosal cells with H. py-lori can activate nuclear factor-κB signaling pathway, induce interleukin-8 (IL-8) release, recruit antigen-presenting cells (APCs), and stimulate the host to produce innate and adaptive immune responses, resulting in anti-H. pylori effects in the host. However, the bacterium has the ability to manipulate and disrupt the host immune system, not only by modifying its own structure to avoid recognition by the host immune sys-tem, but also by inhibiting the proliferation and maturation of T and B lymphocytes, promoting T cell apop-tosis, affecting the balance of Th17/Treg differentiation, and inducing the formation of immune tolerance. Furthermore, H. pylori can inhibit Th1 cell-mediated immune responses and promote immune escape by taking up cholesterol, disrupting the cholesterol-rich microdomains of gastric mucosal epithelial cells, and blocking the assembly of interferon-γ (IFN-γ), IL-22 and IL-6 receptors. This paper summarized the H. py-lori-related immune response and immune escape in humans, in hopes of providing reference materials for clinical control and immunotherapy of H. pylori infection.

关键词

幽门螺杆菌 / 免疫识别 / 免疫应答 / 免疫逃逸

Key words

Helicobacter pylori / immune recognition / immune response / immune escape