Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β.
Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β.
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白细胞介素-1（IL-1）是先天免疫的重要介质，但也可促进炎性组织损伤。在慢性感染期间，如结核病，IL-1的有益抗菌作用必须与预防免疫病理学的需要相平衡。通过外源性控制结核分枝杆菌在体内的复制，我们避免了对抗菌免疫的要求，并发现淋巴细胞衍生的干扰素-γ（IFN-γ）抑制IL-1的产生和感染诱导的免疫病理学。这种作用是由一氧化氮（NO）介导的，我们发现它通过巯基亚硝基化特异性抑制NLRP 3炎性体的组装。这些数据表明，作为适应性免疫的结果产生的NO在调节持续感染期间引起的破坏性先天炎症反应中是不可或缺的。
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 to specifically inhibit the assembly of the NLRP3 inflammasome via thiol nitrosylation. These data suggest that the NO produced as a result of adaptive immunity is indispensable in modulating the destructive innate inflammatory responses that are elicited during persistent infections.
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