Department of Immunology, School of Medicine, Shenzhen University, Shenzhen, China.
Technological Center, Changchun Customs, Changchun, China.
Front Immunol. 2022 Mar 2;13:816378. doi: 10.3389/fimmu.2022.816378. eCollection 2022.
Succinate is at the crossroads of multiple metabolic pathways and plays a role in several immune responses acting as an inflammation signal. However, whether succinate regulates antiviral immune response remains unclear. Here, we found that the production of succinate was reduced in RAW264.7 cells during vesicular stomatitis virus (VSV) infection. Using diethyl succinate to pretreat the mouse peritoneal macrophages and RAW264.7 cells before VSV infection, the production of interferon-β (IFN-β), chemokine (C-X-C motif) ligand 10 (CXCL-10), and IFN-stimulated genes 15 (ISG15) was significantly decreased, following which the VSV replication in diethyl succinate-pretreated cells was obviously increased. Moreover, succinate decreased the expression of IFN-β in serum, lung, and spleen derived from the VSV-infected mice. The overall survival rate in the VSV-infected mice with diethyl succinate pretreatment was also remarkably downregulated. Furthermore, we identified that succinate inhibited the activation of MAVS-TBK1-IRF3 signaling by suppressing the formation of MAVS aggregates. Our findings provide previously unrecognized roles of succinate in antiviral immune response and establish a novel link between metabolism and innate immune response.
琥珀酸处于多种代谢途径的十字路口，在作为炎症信号的几种免疫反应中发挥作用。然而，琥珀酸是否调节抗病毒免疫反应尚不清楚。在这里，我们发现在水疱性口炎病毒（VSV）感染期间 RAW264.7 细胞中琥珀酸的产生减少。在用二乙基琥珀酸预处理小鼠腹腔巨噬细胞和 RAW264.7 细胞后再进行 VSV 感染，干扰素-β（IFN-β）、趋化因子（C-X-C 基序）配体 10（CXCL-10）和干扰素刺激基因 15（ISG15）的产生明显减少，随后二乙基琥珀酸预处理细胞中的 VSV 复制明显增加。此外，琥珀酸降低了来自 VSV 感染小鼠的血清、肺和脾脏中 IFN-β 的表达。用二乙基琥珀酸预处理感染 VSV 的小鼠的总存活率也明显下调。此外，我们发现琥珀酸通过抑制 MAVS 聚集物的形成来抑制 MAVS-TBK1-IRF3 信号的激活。我们的研究结果提供了琥珀酸在抗病毒免疫反应中的以前未被认识到的作用，并在代谢和先天免疫反应之间建立了新的联系。
