Mitochondrial Transcription Factor A Regulates Mycobacterium bovis–Induced IFN-β Production by Modulating Mitochondrial DNA Replication in Macrophages

BACKGROUND: 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. METHODS: In the current study, we investigated the role of TFAM in the production of IFN-β in M. bovis-infected macrophages. RESULTS: 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. CONCLUSIONS: 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.