Role of Interleukin 36γ in Host Defense Against Tuberculosis
Role of Interleukin 36γ in Host Defense Against Tuberculosis
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DOI：
10.1093/infdis/jiw152
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发表时间：
2016-08-01
影响因子：
6.4
通讯作者：
Maertzdorf, Jeroen
中科院分区：
文献类型：
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作者：
Ahsan, Fadhil;Moura-Alves, Pedro;Maertzdorf, Jeroen
结核病仍然是世界范围内的主要杀手，尤其是因为我们对保护性和致病免疫机制的了解不够全面。白介素1(IL-1)和白介素18(IL-18)途径在宿主防御中的作用以及它们通过炎性小体复合体的调节作用已经得到很好的证实。相比之下，白介素36-γ(IL-36-γ)是最近被描述的IL-1家族的一个成员，它的调节及其在宿主防御中的免疫学相关性在很大程度上仍不清楚。在这里，我们显示结核分枝杆菌感染巨噬细胞以两阶段调节的方式诱导IL-36伽马的产生。在第一阶段，微生物配体触发宿主Toll样受体和MyD88依赖的途径，导致IL-36伽马分泌。在第二阶段，内源性IL-1β和IL-18进一步放大IL-36的伽马合成。IL-36γ诱导的抗菌肽和IL-36受体依赖的抑制结核分枝杆菌生长的作用证明了该细胞因子在控制结核分枝杆菌中的相关性。因此，我们首次洞察了促炎细胞因子IL-36γ在结核病过程中的诱导和调节。
Tuberculosis remains a major killer worldwide, not the least because of our incomplete knowledge of protective and pathogenic immune mechanism. The roles of the interleukin 1 (IL-1) and interleukin 18 pathways in host defense are well established, as are their regulation through the inflammasome complex. In contrast, the regulation of interleukin 36 gamma (IL-36 gamma), a recently described member of the IL-1 family, and its immunological relevance in host defense remain largely unknown. Here we show that Mycobacterium tuberculosis infection of macrophages induces IL-36 gamma production in a 2-stage-regulated fashion. In the first stage, microbial ligands trigger host Toll-like receptor and MyD88-dependent pathways, leading to IL-36 gamma secretion. In the second stage, endogenous IL-1 beta and interleukin 18 further amplify IL-36 gamma synthesis. The relevance of this cytokine in the control of M. tuberculosis is demonstrated by IL-36 gamma-induced antimicrobial peptides and IL-36 receptor-dependent restriction of M. tuberculosis growth. Thus, we provide first insight into the induction and regulation of the proinflammatory cytokine IL-36 gamma during tuberculosis.