Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO , USA.
Front Immunol. 2014 Sep 8;5:428. doi: 10.3389/fimmu.2014.00428. eCollection 2014.
WHEN AN ANTIVIRAL IMMUNE RESPONSE IS GENERATED, A BALANCE MUST BE REACHED BETWEEN TWO OPPOSING PATHWAYS: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). Nitric oxide (NO) production by iNOS is an important proinflammatory mediator, whereas Arg1-expressing macrophages contribute to the resolution of inflammation and wound repair. In the context of viral infections, expression of these enzymes can result in a variety of outcomes for the host. NO has direct antiviral properties against some viruses, whereas during other virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection. Arg1 activity not only has important wound healing functions but can also inhibit the antiviral immune response during some viral infections. Thus, depending on the specific virus and the tissue(s) involved, the activity of both of these arginine-hydrolyzing enzymes can either exacerbate or limit the severity of virus-induced disease. In this review, we will discuss a variety of viral infections, including HIV, SARS-CoV, LCMV, HCV, RSV, and others, where myeloid cells influence the control and clearance of the virus from the host, as well as the severity and resolution of tissue damage, via the activities of iNOS and/or Arg1. Clearly, monocyte/macrophage activation and arginine metabolism will continue to be important areas of investigation in the context of viral infections.
当抗病毒免疫反应产生时，必须在两种对立途径之间达到平衡：一是产生促炎和细胞毒性效应物，以驱动强大的抗病毒免疫反应来控制感染；二是产生调节剂，以限制或缓和过度的免疫反应，从而最大限度地减少免疫介导的病理损伤和组织修复。髓系细胞，包括单核细胞和巨噬细胞，在这种平衡中起着重要作用，特别是通过精氨酸水解酶一氧化氮合酶 2（Nos2；iNOS）和精氨酸酶 1（Arg1）的活性。iNOS 产生的一氧化氮（NO）是一种重要的促炎介质，而表达 Arg1 的巨噬细胞有助于炎症的消退和伤口修复。在病毒感染的情况下，这些酶的表达可能会对宿主产生各种结果。NO 对某些病毒具有直接的抗病毒特性，而在其他病毒感染中，NO 可介导免疫病理和/或抑制抗病毒免疫反应，从而促进慢性感染。Arg1 活性不仅具有重要的伤口愈合功能，而且在某些病毒感染中还可以抑制抗病毒免疫反应。因此，具体取决于特定的病毒和涉及的组织，这两种精氨酸水解酶的活性既可以加重也可以限制病毒引起的疾病的严重程度。在这篇综述中，我们将讨论各种病毒感染，包括 HIV、SARS-CoV、LCMV、HCV、RSV 等，其中髓系细胞通过 iNOS 和/或 Arg1 的活性影响宿主对病毒的控制和清除，以及组织损伤的严重程度和恢复。显然，单核细胞/巨噬细胞的激活和精氨酸代谢将继续成为病毒感染背景下的重要研究领域。
