Cadwell Ken, Abraham Clara, Bel Shai, Chauhan Santosh, Coers Jörn, Colombo María I, Davis Jacob R, Hofius Daniel, Nguyen Hang Thi Thu, Ogawa Michinaga, Roy Craig R, Shao Feng, Shizukuishi Sayaka, Stallings Christina L, Szczesna Magdalena, Taylor Gergory, Thurston Teresa Lm, Watson Robert, Wileman Thomas, Xu Yue, Zamboni Dario S
Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
Autophagy Rep. 2025 Sep 1;4(1):2542904. doi: 10.1080/27694127.2025.2542904. eCollection 2025.
Autophagy is an evolutionarily conserved cellular process that is prominent during bacterial infections. In this review article, we discuss how direct pathogen clearance via xenophagy and regulation of inflammatory products represent dual functions of autophagy that coordinate an effective antimicrobial response. We detail the molecular mechanisms of xenophagy, including signals that indicate the presence of an intracellular pathogen and autophagy receptor-mediated cargo targeting, while highlighting pathogen counterstrategies, such as bacterial effector proteins that inhibit autophagy initiation or exploit autophagic membranes for replication. Pathways that are related to autophagy, including LC3-associated phagocytosis (LAP) and conjugation of ATG8 to single membranes (CASM), are expanding the role of autophagy in antimicrobial defense beyond traditional double-membrane autophagosomes. Examination of Crohn disease-associated genes links impaired autophagy to inflammation and defective bacterial handling. We propose emerging concepts, such as effector-triggered immunity, where autophagy inhibition by pathogens triggers inflammatory defenses and discusses the therapeutic potential of modulating autophagy in infectious and inflammatory diseases.
自噬是一种在进化上保守的细胞过程，在细菌感染期间尤为突出。在这篇综述文章中，我们讨论了通过异噬作用直接清除病原体以及调节炎症产物如何代表自噬的双重功能，这两种功能协调了有效的抗菌反应。我们详细阐述了异噬作用的分子机制，包括指示细胞内病原体存在的信号以及自噬受体介导的货物靶向，同时强调了病原体的应对策略，例如抑制自噬起始或利用自噬膜进行复制的细菌效应蛋白。与自噬相关的途径，包括LC3相关吞噬作用（LAP）和ATG8与单膜的结合（CASM），正在将自噬在抗菌防御中的作用扩展到传统的双膜自噬体之外。对克罗恩病相关基因的研究将自噬受损与炎症和细菌处理缺陷联系起来。我们提出了一些新兴概念，如效应器触发的免疫，即病原体对自噬的抑制触发炎症防御，并讨论了在感染性和炎症性疾病中调节自噬的治疗潜力。
