Diethyl succinate pretreatment significantly suppressed the antiviral immune response, resulting in 0% survival at 20 hours post-VSV infection compared to 75% survival in control mice.
Does diethyl succinate pretreatment suppress the antiviral immune response in VSV-infected cells and mice?
Succinate acts as a natural suppressor of the antiviral immune response by inhibiting MAVS aggregation, establishing a link between metabolism and innate immunity.
Absolute Event Rate: 0% vs 75%
p-value: p=<0.001
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.
Xiao et al. (Wed,) conducted a other in Vesicular stomatitis virus (VSV) infection. Diethyl succinate vs. PBS or DMSO was evaluated on Overall survival in VSV-infected mice at 20 hours (p=<0.001). Diethyl succinate pretreatment significantly suppressed the antiviral immune response, resulting in 0% survival at 20 hours post-VSV infection compared to 75% survival in control mice.