The mitochondrial network plays a critical role in the regulation of innate immune signaling and subsequent production of proinflammatory cytokines such as IFN-β and IL-1β. Dynamin-related protein 1 (DRP1) promotes mitochondrial fission and quality control to maintain cellular homeostasis during infection. However, mechanisms by which DRP1 and mitochondrial dynamics control innate immune signaling and the proinflammatory response are incompletely understood. Here we show that macrophage DRP1 is a positive regulator of TNF-α production during sterile inflammation or bacterial infection. Silencing macrophage DRP1 decreased mitochondrial fragmentation and TNF-α production upon stimulation with lipopolysaccharide (LPS) or methicillin-resistant Staphylococcus aureus (MRSA) infection. The defect in TNF-α induction could not be attributed to changes in gene expression. Instead, DRP1 was required for post-transcriptional control of TNF-α. In contrast, silencing DRP1 enhanced IL-6 and IL-1β production, indicating a distinct mechanism for DRP1-dependent TNF-α regulation. Our results highlight DRP1 as a key player in the macrophage pro-inflammatory response and point to its involvement in post-transcriptional control of TNF-α production.

线粒体网络在先天免疫信号的调控以及随后的促炎细胞因子（如IFN-β和IL-1β）的产生中起着至关重要的作用。动力相关蛋白1（DRP1）促进线粒体分裂和质量控制，以在感染过程中维持细胞稳态。但是，尚不完全了解DRP1和线粒体动力学控制先天免疫信号转导和促炎反应的机制。在这里，我们显示巨噬细胞DRP1是无菌炎症或细菌感染过程中TNF-α产生的正调节剂。沉默巨噬细胞DRP1减少脂多糖（LPS）或耐甲氧西林的刺激后线粒体片段化和TNF-α的产生金黄色葡萄球菌（MRSA）感染。TNF-α诱导的缺陷不能归因于基因表达的变化。取而代之的是，转录后控制TNF-α需要DRP1。相反，沉默DRP1可增强IL-6和IL-1β的产生，表明DRP1依赖性TNF-α调节的独特机制。我们的结果突出了DRP1在巨噬细胞促炎反应中的关键作用，并指出其参与TNF-α产生的转录后控制。