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TREM-1 enhances Mycobacterium tuberculosis-induced inflammatory responses in macrophages
Microbes and Infection ( IF 2.6 ) Pub Date : 2020-10-10 , DOI: 10.1016/j.micinf.2020.10.001
Jia-Yih Feng, Wei-Juin Su, Fan-Yi Chuang, Sheng-Wei Pan, Yi-Chen Yeh, Yung-Yang Lin, Nien-Jung Chen

Triggering receptor expressed on myeloid cells 1 (TREM-1) extensively interacts with toll-like receptors and amplifies pro-inflammatory responses. The effect of TREM-1 on Mycobacterium tuberculosis (MTB)-related immune responses remains to be elucidated. We isolated bone marrow-derived macrophages (BMDMs) from wild-type mice and Trem-1 KO mice and treated them with MTB whole cell lysate and EsxA (ESAT-6). Cytokine production and mRNA expression, including Trem-1, following stimulation were evaluated. Intratracheal instillation of heat-killed MTB (HKMTB) in mice was performed and the presence of TREM-1-positive macrophages was investigated by immunohistochemistry analysis. In our study, BMDMs isolated from wild-type mice produced more pro-inflammatory cytokines and demonstrated higher inflammatory gene expression levels compared with those isolated from Trem-1 KO mice when stimulated with MTB whole cell lysate. EsxA had a synergistic effect with MTB whole cell lysate on the induction of pro-inflammatory responses. The gene expression of Trem-1 was upregulated when treated with MTB-related proteins. TREM-1-positive macrophages were identified in the lung tissues from patients with active TB and from wild-type mice treated with intratracheal instillation of HKMTB. In conclusion, in mouse macrophages, TREM-1 could enhance pro-inflammatory immune responses when stimulated with MTB-related proteins. The gene expression of Trem-1 could also be induced by MTB-related stimulation.



中文翻译:

TREM-1增强巨噬细胞中结核分枝杆菌诱导的炎症反应

骨髓细胞上表达的触发受体 1 (TREM-1) 与 toll 样受体广泛相互作用并放大促炎反应。TREM-1 对结核分枝杆菌(MTB) 相关免疫反应的影响仍有待阐明。我们从野生型小鼠和Trem-1 KO 小鼠中分离出骨髓来源的巨噬细胞 (BMDM),并用 MTB 全细胞裂解物和 EsxA (ESAT-6) 处理它们。细胞因子产生和 mRNA 表达,包括Trem-1,以下刺激进行了评估。对小鼠进行了热灭活 MTB (HKMTB) 的气管内滴注,并通过免疫组织化学分析研究了 TREM-1 阳性巨噬细胞的存在。在我们的研究中,当用 MTB 全细胞裂解物刺激时,从野生型小鼠中分离的 BMDM 产生更多的促炎细胞因子,并且与从Trem-1 KO 小鼠中分离的那些相比,表现出更高的炎症基因表达水平。EsxA 与 MTB 全细胞裂解物对促炎反应的诱导具有协同作用。Trem-1的基因表达当用 MTB 相关蛋白处理时被上调。在活动性结核病患者和经气管内滴注 HKMTB 治疗的野生型小鼠的肺组织中鉴定出 TREM-1 阳性巨噬细胞。总之,在小鼠巨噬细胞中,当用 MTB 相关蛋白刺激时,TREM-1 可以增强促炎免疫反应。山地车相关刺激也可以诱导Trem-1的基因表达。

更新日期:2020-10-10
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