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

Abstract

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.