Accumulation of EBI3 induced by virulent Mycobacterium tuberculosis inhibits apoptosis in murine macrophages
Accumulation of EBI3 induced by virulent Mycobacterium tuberculosis inhibits apoptosis in murine macrophages
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强毒力结核杆菌诱导的 EBI3 积累抑制小鼠巨噬细胞凋亡
DOI：
10.1093/femspd/ftz007
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发表时间：
2019-02-01
影响因子：
3.3
通讯作者：
Pan, Qin
中科院分区：
文献类型：
--
作者：
Deng, Jia-Hui;Chen, Han-Yu;Pan, Qin
巨噬细胞是结核分枝杆菌（M. tuberculosis）的主要宿主靶细胞。tb）。作为免疫调节细胞因子IL-27和IL-35的亚基，EB病毒诱导的基因3（EBI 3）通常以分泌形式进行探索，并根据其由细胞外EBI 3触发的作用进行评估。然而，对细胞内EBI 3功能知之甚少。在目前的研究中，我们报告说，结核病患者中巨噬细胞产生的EBI 3升高。我们进一步证明了EBI 3在毒性M. TB处理的鼠巨噬细胞。真核翻译延伸因子1-α 1（eEF 1A 1）与细胞内EBI 3结合，减少EBI 3的Lys 48（K48）连接的泛素化，导致EBI 3积累。此外，胞内EBI 3抑制caspase-3介导的M. TB处理的巨噬细胞。在此，我们提出了一种新的机制，积累细胞内EBI 3和巨噬细胞凋亡的调节响应于有毒M。TB.
Macrophages are the primary host target cells of Mycobacterium tuberculosis (M. tb). As a subunit of immunoregulatory cytokines IL-27 and IL-35, Epstein-Barr virus-induced gene 3 (EBI3) has typically been explored as the secreted form and assessed in terms of its effects triggered by extracellular EBI3. However, little is known about intracellular EBI3 function. In the current study, we report that EBI3 production by macrophages is elevated in TB patients. We further demonstrate that increased EBI3 accumulates in virulent M. tb-treated murine macrophages. Eukaryotic translation elongation factor 1-alpha 1 (eEF1A1) binds to intracellular EBI3 to reduce Lys48 (K48)-linked ubiquitination of EBI3, leading to EBI3 accumulation. Moreover, the intracellular EBI3 inhibits caspase-3-mediated apoptosis in M. tb-treated macrophages. Herein, we propose a novel mechanism for accumulating intracellular EBI3 and its regulation of macrophage apoptosis in response to virulent M. tb.