IL-37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2-like Phenotype
IL-37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2-like Phenotype
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DOI：
10.1111/sji.12326
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发表时间：
2015-10-01
影响因子：
3.7
通讯作者：
Wang, Q.
中科院分区：
文献类型：
--
作者：
Huang, Z.;Gao, C.;Wang, Q.
白细胞介素-37（IL-37）是IL-1家族的成员，主要用作抗炎细胞因子，减少炎症和抑制免疫应答。然而，IL-37在结核病（TB）中的表达和作用仍不清楚。我们的目的是测量25例活动性TB患者的血清IL-37和几种重要细胞因子水平，并分析其与疾病活动性的关系。我们发现结核病患者的IL-37水平降低，并在治疗后恢复。IL-37水平与IFN-γ和IL-12呈负相关，而与IL-10和TGF-β水平呈正相关。在IL-37后，活动性TB患者的外周血单核细胞分泌被阻断，IFN-γ和IL-10的产生显著上调;这在健康供体或治疗后的患者中未观察到。IL-37敲低显著增强THP 1衍生的巨噬细胞对结核分枝杆菌（M.tb）的吞噬活性。同时检测M1/M2极化相关标志物，IL-37诱导THP 1衍生的巨噬细胞向高CD 206（+）和低CD 86（+）巨噬细胞亚型的表型转变。此外，这种表型转变伴随着M2巨噬细胞的特征性标志--β-淀粉酶1、TGF-β和IL-10的mRNA水平上调。总之，我们的研究结果表明，TB患者中IL-37水平的增加与IFN-γ、IL-12、IL-10和TGF-β水平相关，并且IL-37通过抑制促炎细胞因子的产生和诱导巨噬细胞朝向M2样表型而在TB感染中起病理作用。因此，IL-37可能成为了解结核病发病机制的新的研究靶点。
Interleukin-37 (IL-37), a member of the IL-1 family, primarily functions as an anti-inflammatory cytokine, reducing inflammation and suppressing the immune response. However, the expression and role of IL-37 in tuberculosis (TB) remains unknown. We aimed to measure serum levels of IL-37 and several important cytokines in 25 patients with active TB and to analyse their association with disease activity. We found that IL-37 levels decreased in patients with TB and recovered after treatment. IL-37 levels negatively correlated with the serum concentration of IFN- and IL-12 but positively correlated with IL-10 and TGF- levels. After IL-37, secretion was blocked in peripheral blood mononuclear cells from active patients with TB, IFN- and IL-10 production was significantly upregulated; this was not observed in healthy donors or patients after treatment. IL-37 knockdown significantly enhanced the phagocytic activity of THP1-derived macrophages towards Mycobacterium tuberculosis (M.tb). M1/M2 polarization-associated markers were detected simultaneously, and IL-37 induced a phenotypic shift in THP1-derived macrophages towards a high CD206(+) and low CD86(+) macrophage subtype. Furthermore, this phenotypic shift was accompanied by upregulated mRNA levels of arginase 1, TGF- and IL-10, which are characteristic hallmarks of M2 macrophages. In conclusion, our results suggest that increased levels of IL-37 in patients with TB are associated with IFN-, IL-12, IL-10 and TGF- levels and that IL-37 plays a pathological role in TB infection by inhibiting the production of pro-inflammatory cytokines and inducing macrophages towards an M2-like phenotype. Thus, IL-37 may be a novel research target to understand the pathogenesis of TB infection.