IL-37 Confers Protection against Mycobacterial Infection Involving Suppressing Inflammation and Modulating T Cell Activation.
IL-37 Confers Protection against Mycobacterial Infection Involving Suppressing Inflammation and Modulating T Cell Activation.
复制标题
DOI：
10.1371/journal.pone.0169922
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ge B
中科院分区：
文献类型：
--
作者：
Liu H;Zheng R;Wang P;Yang H;He X;Ji Q;Bai W;Chen H;Chen J;Peng W;Liu S;Liu Z;Ge B
白细胞介素-37（IL-37）是IL-1家族的一个新成员，通过广泛降低先天性炎症和获得性免疫而发挥重要的免疫抑制作用，但其是否参与结核病的发病机制尚未明确。在这项研究中，单核苷酸多态性（SNP）分析表明IL-37的遗传变异rs3811047与TB易感性相关。与先前的报道一致，与健康对照相比，在TB患者中观察到血清中IL-37丰度显著升高，外周血单核细胞（PBMC）中IL-37蛋白表达增加。此外，在结核分枝杆菌（Mtb）感染的巨噬细胞或BCG感染的小鼠肺中检测到IL-37的释放，同时减少促炎细胞因子（包括IL-6和TNF-α）的产生。此外，与野生型小鼠相比，BCG感染的IL-37-Tg小鼠表现出肺中分枝杆菌负荷和组织损伤减少，伴随着脾中Th 1细胞的频率较高，调节性T细胞和Th 17细胞的频率较低。综上所述，我们的发现表明IL-37赋予对Mtb感染的抗性，可能涉及抑制有害炎症和调节T细胞应答。提示IL-37可能成为结核病治疗和诊断的新分子靶点。
Interleukin-37 (IL-37), a novel member of the IL-1 family, plays fundamental immunosuppressive roles by broadly reducing both innate inflammation and acquired immunity, but whether it is involved in the pathogenesis of tuberculosis (TB) has not been clearly elucidated. In this study, single nucleotide polymorphism (SNP) analysis demonstrated an association of the genetic variant rs3811047 of IL-37 with TB susceptibility. In line with previous report, a significant elevated IL-37 abundance in the sera and increased expression of IL-37 protein in the peripheral blood mononuclear cells (PBMC) were observed in TB patients in comparison to healthy controls. Moreover, release of IL-37 were detected in either macrophages infected with Mycobacterium tuberculosis (Mtb) or the lung of BCG-infected mice, concurrent with reduced production of proinflammatory cytokines including IL-6 and TNF-α. Furthermore, in contrast to wild-type mice, BCG-infected IL-37-Tg mice manifested with reduced mycobacterial burden and tissue damage in the lung, accompanied by higher frequency of Th1 cell and less frequencies of regulatory T cells and Th17 cells in the spleen. Taken together, our findings demonstrated that IL-37 conferred resistance to Mtb infection possibly involving suppressing detrimental inflammation and modulating T cell responses. These findings implicated that IL-37 may be employed as a new molecular target for the therapy and diagnosis of TB.