Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
J Infect Dis. 2020 Jan 14;221(3):438-448. doi: 10.1093/infdis/jiz461.
Mycobacterium bovis persistently survives in macrophages by developing multiple strategies to evade host immune responses, and the early induction of interferon-β (IFN-β) is one of these critical strategies. The mitochondrial transcription factor A (TFAM) plays a vital role in mitochondrial DNA (mtDNA) metabolism and has been suggested to influence IFN-β production in response to viral infection. However, its role in the production of IFN-β by M. bovis has not been elucidated.
In the current study, we investigated the role of TFAM in the production of IFN-β in M. bovis-infected macrophages.
We found that knockdown of TFAM expression significantly reduced M. bovis-induced IFN-β production, mtDNA copy numbers and cytosolic mtDNA were increased in murine macrophages with M. bovis infection, cytosolic mtDNA contributed to IFN-β production, and TFAM was required for the increase in mtDNA copy numbers induced by M. bovis. We also observed that TFAM affected the intracellular survival of M. bovis.
Our results suggest that TFAM plays an essential role in M. bovis-induced IFN-β production by regulating mtDNA copy numbers. This might be a new strategy adopted by M. bovis for its intracellular survival.
牛分枝杆菌通过开发多种策略来逃避宿主免疫反应而在巨噬细胞中持续生存，早期诱导干扰素-β（IFN-β）是这些关键策略之一。线粒体转录因子 A（TFAM）在线粒体 DNA（mtDNA）代谢中发挥重要作用，并被认为会影响病毒感染后 IFN-β的产生。然而，其在牛分枝杆菌诱导 IFN-β产生中的作用尚未阐明。
在本研究中，我们研究了 TFAM 在牛分枝杆菌感染的巨噬细胞中产生 IFN-β中的作用。
我们发现，TFAM 表达的敲低显著降低了牛分枝杆菌诱导的 IFN-β产生，牛分枝杆菌感染的小鼠巨噬细胞中 mtDNA 拷贝数和胞质 mtDNA 增加，胞质 mtDNA 有助于 IFN-β的产生，而 TFAM 是牛分枝杆菌诱导的 mtDNA 拷贝数增加所必需的。我们还观察到 TFAM 影响了牛分枝杆菌的细胞内存活。
我们的结果表明，TFAM 通过调节 mtDNA 拷贝数在牛分枝杆菌诱导的 IFN-β产生中发挥重要作用。这可能是牛分枝杆菌在细胞内生存的一种新策略。
