TFAM regulates Mycobacterium bovis-induced IFN-β production by modulating mtDNA replication in macrophages.

BACKGROUND: Mycobacterium bovis (M. bovis) persistently survives in macrophages by developing multiple strategies to evade host immune responses, and the early induction of interferon beta (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, the role of TFAM 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; that increased mtDNA copy number and cytosolic mtDNA in murine macrophage upon M. bovis infection; that cytosolic mtDNA contributed to IFN-β production and that TFAM was required for the increase of mtDNA copy number induced by M. bovis. Furthermore, we 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 through regulating mtDNA copy number. This might be a new strategy adopted by M. bovis for its intracellular survival.