Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Curr Opin Microbiol. 2020 Apr;54:1-10. doi: 10.1016/j.mib.2020.01.003. Epub 2020 Jan 31.
The gastric bacterium Helicobacter pylori efficiently evades innate immune detection and persistently colonizes its human host. Understanding the genetic determinants that H. pylori uses to establish and maintain persistence, along with their cellular targets, is key to our understanding of the pathogenesis of this extraordinarily successful bacterial colonizer of the human stomach. This review highlights recent advances in elucidating innate immune recognition of H. pylori, its interactions with myeloid cells and the consequences that this very local infection has for immune responses at extragastric sites in models of allergy, autoimmunity and parasitic infection. The human-specific, gram-negative gastric colonizer and carcinogen H. pylori represents the prototype of a persistent bacterial pathogen. It is transmitted during early childhood, typically from mother to infant, and is believed to persist in its human host from the cradle to the grave. The tremendous success of H. pylori in infecting and colonizing half of the world's population, and in continuously accompanying humans since they migrated out of Africa over 60000 years ago, can largely be attributed to its ability to manipulate the host immune system to its own advantage, and to thereby ensure its own persistence and chronicity. In his final years as an active PI, Stanley Falkow increasingly recognized the need to understand bacterial persistence strategies as a prerequisite of understanding the pathogenesis of chronic bacterial infections, and, inspired in large part by Denise Monack's work on Salmonella persistence, many of our discussions at the time revolved around this topic. Multiple labs have since made important contributions to our understanding of innate immune detection of H. pylori, the types and polarization of adaptive immune responses that ensue, the ability of H. pylori to skew such immune responses to its advantage, and its ability to manipulate the host immune system with far-reaching, even systemic consequences. This review attempts to cover some of these topics, with a particular focus on the most recent contributions by researchers in the field.
幽门螺杆菌（Helicobacter pylori）是一种胃部细菌，它能有效地逃避先天免疫检测，并持续定植于其人类宿主中。了解幽门螺杆菌用于建立和维持持续性的遗传决定因素，以及它们的细胞靶标，是理解这种在人类胃部极为成功的细菌定植体的发病机制的关键。本综述重点介绍了阐明幽门螺杆菌先天免疫识别、它与髓样细胞相互作用以及这种非常局部感染对过敏、自身免疫和寄生虫感染模型中外周部位免疫反应的影响方面的最新进展。人类特有的革兰氏阴性胃部定植菌和致癌物幽门螺杆菌代表了持续性细菌病原体的原型。它在儿童早期传播，通常是从母亲到婴儿，并且据信自人类从非洲迁移以来，它一直存在于人类宿主中，从婴儿期到死亡。幽门螺杆菌感染和定植世界一半人口的巨大成功，以及自 6 万多年前人类从非洲迁移以来一直持续伴随着人类，可以在很大程度上归因于它操纵宿主免疫系统为自身利益服务的能力，从而确保其自身的持久性和慢性。在作为活跃的首席研究员的最后几年里，斯坦利·福尔科（Stanley Falkow）越来越认识到需要理解细菌持久性策略，作为理解慢性细菌感染发病机制的先决条件，并且在很大程度上受到丹尼斯·莫纳克（Denise Monack）关于沙门氏菌持久性的工作的启发，我们当时的许多讨论都围绕着这个主题展开。此后，多个实验室为我们理解幽门螺杆菌的先天免疫检测、随之而来的适应性免疫反应的类型和极化、幽门螺杆菌将这种免疫反应偏向其优势的能力以及它操纵宿主免疫系统的能力做出了重要贡献，其影响甚至具有系统性。本综述试图涵盖其中的一些主题，特别关注该领域研究人员的最新贡献。
