Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Nat Immunol. 2013 Jan;14(1):52-60. doi: 10.1038/ni.2474. Epub 2012 Nov 18.
Interleukin 1 (IL-1) is an important mediator of innate immunity but can also promote inflammatory tissue damage. During chronic infections such as tuberculosis, the beneficial antimicrobial role of IL-1 must be balanced with the need to prevent immunopathology. By exogenously controlling the replication of Mycobacterium tuberculosis in vivo, we obviated the requirement for antimicrobial immunity and discovered that both IL-1 production and infection-induced immunopathology were suppressed by lymphocyte-derived interferon-γ (IFN-γ). This effect was mediated by nitric oxide (NO), which we found specifically inhibited assembly of the NLRP3 inflammasome via thiol nitrosylation. Our data indicate that the NO produced as a result of adaptive immunity is indispensable in modulating the destructive innate inflammatory responses elicited during persistent infections.
白细胞介素 1（IL-1）是先天免疫的重要介质，但也可促进炎症性组织损伤。在结核病等慢性感染中，必须平衡 IL-1 的有益抗微生物作用与预防免疫病理的需要。通过体外控制结核分枝杆菌的复制，我们排除了对抗微生物免疫的需求，并发现白细胞介素 1 的产生和感染引起的免疫病理都受到淋巴细胞衍生的干扰素-γ（IFN-γ）的抑制。这种作用是由一氧化氮（NO）介导的，我们发现它通过硫醇亚硝基化特异性抑制 NLRP3 炎性体的组装。我们的数据表明，适应性免疫产生的 NO 对于调节持续感染中引发的破坏性先天炎症反应是不可或缺的。
