Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
J Exp Med. 2019 Mar 4;216(3):501-516. doi: 10.1084/jem.20181886. Epub 2019 Feb 21.
The generation of phagosomal cytotoxic reactive species (i.e., free radicals and oxidants) by activated macrophages and neutrophils is a crucial process for the control of intracellular pathogens. The chemical nature of these species, the reactions they are involved in, and the subsequent effects are multifaceted and depend on several host- and pathogen-derived factors that influence their production rates and catabolism inside the phagosome. Pathogens rely on an intricate and synergistic antioxidant armamentarium that ensures their own survival by detoxifying reactive species. In this review, we discuss the generation, kinetics, and toxicity of reactive species generated in phagocytes, with a focus on the response of macrophages to internalized pathogens and concentrating on and as examples of bacterial and parasitic infection, respectively. The ability of pathogens to deal with host-derived reactive species largely depends on the competence of their antioxidant networks at the onset of invasion, which in turn can tilt the balance toward pathogen survival, proliferation, and virulence over redox-dependent control of infection.
活性巨噬细胞和中性粒细胞产生吞噬细胞毒性反应性物质（即自由基和氧化剂）是控制细胞内病原体的关键过程。这些物质的化学性质、它们所参与的反应以及随后的影响是多方面的，取决于几个宿主和病原体来源的因素，这些因素影响它们在吞噬体中的产生速率和分解代谢。病原体依赖于复杂的协同抗氧化武器库，通过解毒反应性物质来确保自身的存活。在这篇综述中，我们讨论了吞噬细胞中产生的反应性物质的生成、动力学和毒性，重点是巨噬细胞对内化病原体的反应，并集中讨论了 和 ，分别作为细菌和寄生虫感染的例子。病原体处理宿主来源的反应性物质的能力在很大程度上取决于其抗氧化网络在入侵时的能力，这反过来又可以使病原体的生存、增殖和毒力偏向于依赖氧化还原控制感染。
