Paiva Claudia N, Bozza Marcelo T
Departamento de Imunologia, Instituto de Microbiologia , CCS Bloco D, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil .
Antioxid Redox Signal. 2014 Feb 20;20(6):1000-37. doi: 10.1089/ars.2013.5447. Epub 2013 Oct 26.
Reactive oxygen species (ROS) are deadly weapons used by phagocytes and other cell types, such as lung epithelial cells, against pathogens. ROS can kill pathogens directly by causing oxidative damage to biocompounds or indirectly by stimulating pathogen elimination by various nonoxidative mechanisms, including pattern recognition receptors signaling, autophagy, neutrophil extracellular trap formation, and T-lymphocyte responses. Thus, one should expect that the inhibition of ROS production promote infection. Increasing evidences support that in certain particular infections, antioxidants decrease and prooxidants increase pathogen burden. In this study, we review the classic infections that are controlled by ROS and the cases in which ROS appear as promoters of infection, challenging the paradigm. We discuss the possible mechanisms by which ROS could promote particular infections. These mechanisms are still not completely clear but include the metabolic effects of ROS on pathogen physiology, ROS-induced damage to the immune system, and ROS-induced activation of immune defense mechanisms that are subsequently hijacked by particular pathogens to act against more effective microbicidal mechanisms of the immune system. The effective use of antioxidants as therapeutic agents against certain infections is a realistic possibility that is beginning to be applied against viruses.
活性氧(ROS)是吞噬细胞和其他细胞类型(如肺上皮细胞)用于对抗病原体的致命武器。ROS可通过对生物化合物造成氧化损伤直接杀死病原体,或通过刺激各种非氧化机制(包括模式识别受体信号传导、自噬、中性粒细胞胞外陷阱形成和T淋巴细胞反应)来间接促进病原体的清除。因此,人们可能会认为抑制ROS的产生会促进感染。越来越多的证据支持,在某些特定感染中,抗氧化剂会降低病原体负担,而促氧化剂则会增加病原体负担。在本研究中,我们回顾了由ROS控制的经典感染以及ROS表现为感染促进因素的案例,对这一范例提出了挑战。我们讨论了ROS促进特定感染的可能机制。这些机制尚不完全清楚,但包括ROS对病原体生理学的代谢影响、ROS对免疫系统的损伤以及ROS诱导的免疫防御机制激活,随后这些机制被特定病原体劫持,以对抗免疫系统更有效的杀菌机制。将抗氧化剂有效用作对抗某些感染的治疗药物是一种现实的可能性,并且已开始应用于对抗病毒。