Department of Immunology, University of Hohenheim, Stuttgart, Germany.
Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Melbourne, VIC, Australia.
Front Immunol. 2022 Jul 28;13:930882. doi: 10.3389/fimmu.2022.930882. eCollection 2022.
Members of the mammalian Nod-like receptor (NLR) protein family are important intracellular sensors for bacteria. Bacteria have evolved under the pressure of detection by host immune sensing systems, leading to adaptive subversion strategies to dampen immune responses for their benefits. These include modification of microbe-associated molecular patterns (MAMPs), interception of innate immune pathways by secreted effector proteins and sophisticated instruction of anti-inflammatory adaptive immune responses. Here, we summarise our current understanding of subversion strategies used by bacterial pathogens to manipulate NLR-mediated responses, focusing on the well-studied members NOD1/2, and the inflammasome forming NLRs NLRC4, and NLRP3. We discuss how bacterial pathogens and their products activate these NLRs to promote inflammation and disease and the range of mechanisms used by bacterial pathogens to evade detection by NLRs and to block or dampen NLR activation to ultimately interfere with the generation of host immunity. Moreover, we discuss how bacteria utilise NLRs to facilitate immunotolerance and persistence in the host and outline how various mechanisms used to attenuate innate immune responses towards bacterial pathogens can also aid the host by reducing immunopathologies. Finally, we describe the therapeutic potential of harnessing immune subversion strategies used by bacteria to treat chronic inflammatory conditions.
哺乳动物核苷酸结合寡聚化结构域样受体（NLR）蛋白家族成员是细菌的重要细胞内传感器。细菌在宿主免疫感应系统检测的压力下进化，导致适应性颠覆策略，以减轻免疫反应以获取利益。这些策略包括微生物相关分子模式（MAMPs）的修饰、分泌效应蛋白对固有免疫途径的拦截以及对抗炎适应性免疫反应的复杂指令。在这里，我们总结了我们目前对细菌病原体用于操纵 NLR 介导的反应的颠覆策略的理解，重点关注研究得很好的成员 NOD1/2，以及形成 NLRP3 的炎症小体形成 NLRs NLRC4。我们讨论了细菌病原体及其产物如何激活这些 NLR 以促进炎症和疾病，以及细菌病原体用于逃避 NLR 检测并阻断或抑制 NLR 激活以最终干扰宿主免疫的产生的一系列机制。此外，我们讨论了细菌如何利用 NLR 促进宿主中的免疫耐受和持久性，并概述了用于减弱针对细菌病原体的固有免疫反应的各种机制如何通过减少免疫病理来帮助宿主。最后，我们描述了利用细菌用于治疗慢性炎症性疾病的免疫颠覆策略的治疗潜力。
