Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Shandong University, Jinan, Shandong, China.
Key Laboratory for Experimental Teratology of Ministry of Education and Department of Cell Biology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Free Radic Biol Med. 2024 Aug 20;221:52-63. doi: 10.1016/j.freeradbiomed.2024.05.015. Epub 2024 May 14.
Virus infection is a major threat to human health and remains a significant cause of death to date. Macrophages are important innate immune cells that exhibit indispensable roles in controlling virus replication. It was recently reported that metabolic adaption determines the functional state of macrophages. Thus, to further unravel the crucial factors involving in metabolic adaption of macrophages might provide the potential candidates for optimizing their anti-viral capabilities.
RT-PCR, Western blotting, virus plaque assay and HE were used to evaluate the viral load in virus-infected Tipe1 and Tipe1 mice or cultured macrophages. RNA sequencing were performed with Tipe1or Tipe1 BMDMs upon virus infection. Extracellular acidification rate (ECAR) was applied for analyzing glycolysis rate in virus-infected BMDMs. Co-immunoprecipitation (Co-IP) assay and LC-MS/MS were used to determine the potential interacting proteins of TIPE1.
TIPE1 level was significantly reduced in BMDMs infected with either RNA viruses or DNA virus. Deficiency of Tipe1 in macrophages increased viral load and aggravated tissue damage. Mechanistically, TIPE1 suppressed the glycolytic capacity of macrophages through interacting with PKM2 and promoting its ubiquitination degradation, which in turn decreased HIF1α transcription and viral replication in macrophages.
TIPE1 functions as a novel regulator for metabolic reprogramming and virus infection in macrophages.
病毒感染是对人类健康的主要威胁，也是迄今为止导致死亡的主要原因。巨噬细胞是重要的先天免疫细胞，在控制病毒复制方面发挥着不可或缺的作用。最近有报道称，代谢适应决定了巨噬细胞的功能状态。因此，进一步揭示参与巨噬细胞代谢适应的关键因素，可能为优化其抗病毒能力提供潜在的候选因素。
采用 RT-PCR、Western blot、病毒噬斑试验和 HE 染色法检测病毒感染的 Tipe1 和 Tipe1 小鼠或培养的巨噬细胞中的病毒载量。用 RNA 测序法检测病毒感染的 Tipe1 或 Tipe1 BMDMs。用细胞外酸化率（ECAR）测定法分析病毒感染的 BMDMs 中的糖酵解率。采用免疫共沉淀（Co-IP）试验和 LC-MS/MS 测定 TIPE1 的潜在相互作用蛋白。
RNA 病毒或 DNA 病毒感染的 BMDMs 中 TIPE1 水平显著降低。巨噬细胞中 Tipe1 的缺失增加了病毒载量并加重了组织损伤。机制上，TIPE1 通过与 PKM2 相互作用并促进其泛素化降解，抑制巨噬细胞的糖酵解能力，从而降低 HIF1α转录和巨噬细胞中的病毒复制。
TIPE1 作为一种新型调节因子，在巨噬细胞的代谢重编程和病毒感染中发挥作用。
