Macrophages destroy bacteria and other microorganisms through phagocytosis-coupled antimicrobial responses, such as the generation of reactive oxygen species and the delivery of hydrolytic enzymes from lysosomes to the phagosome. However, many intracellular bacteria subvert these responses, escaping to other cellular compartments to survive and/or replicate. Such bacterial subversion strategies are countered by a range of additional direct antibacterial responses that are switched on by pattern-recognition receptors and/or host-derived cytokines and other factors, often through inducible gene expression and/or metabolic reprogramming. Our understanding of these inducible antibacterial defence strategies in macrophages is rapidly evolving. In this Review, we provide an overview of the broad repertoire of antibacterial responses that can be engaged in macrophages, including LC3-associated phagocytosis, metabolic reprogramming and antimicrobial metabolites, lipid droplets, guanylate-binding proteins, antimicrobial peptides, metal ion toxicity, nutrient depletion, autophagy and nitric oxide production. We also highlight key inducers, signalling pathways and transcription factors involved in driving these different antibacterial responses. Finally, we discuss how a detailed understanding of the molecular mechanisms of antibacterial responses in macrophages might be exploited for developing host-directed therapies to combat antibiotic-resistant bacterial infections.

巨噬细胞通过吞噬作用耦合的抗菌反应来破坏细菌和其他微生物，例如产生活性氧以及将水解酶从溶酶体传递到吞噬体。然而，许多细胞内细菌破坏了这些反应，逃逸到其他细胞区室以生存和/或复制。这种细菌颠覆策略被一系列额外的直接抗菌反应所抵消，这些反应通常通过诱导基因表达和/或代谢重编程，由模式识别受体和/或宿主衍生的细胞因子和其他因素开启。我们对巨噬细胞中这些诱导性抗菌防御策略的理解正在迅速发展。在这篇综述中，我们概述了巨噬细胞可能参与的广泛抗菌反应，包括 LC3 相关的吞噬作用、代谢重编程和抗菌代谢物、脂滴、鸟苷酸结合蛋白、抗菌肽、金属离子毒性、营养物质耗竭、自噬和一氧化氮的产生。我们还重点介绍了驱动这些不同抗菌反应的关键诱导物、信号通路和转录因子。最后，我们讨论了如何利用对巨噬细胞抗菌反应分子机制的详细了解来开发针对宿主的疗法来对抗抗生素耐药性细菌感染。