Figure 1.

The schematic diagram is representing the molecular mechanism through which mitochondrial DNA stimulates innate anti-microbial immunity. Under the stress conditions, mitochondrial DNA is released from mitochondria that stimulate the production of pro-inflammatory cytokines (e.g., IL-6, IL-1β, MMP-8, and TNF-α,) and also enhance their release. The escaped mitochondrial DNA following the microbial infection is detected by the cGAS/stimulator of interferon genes (STING) signaling pathway that causes TBK1/IRF3 dependent production of type I interferon and also limits replication of microbes. However, the caspases, e.g., caspase-3, -7, and -9 activation regulates the intrinsic apoptotic signaling pathway. Furthermore, the escaped mitochondrial DNA after stress also stimulates the NLRP3 inflammasome to recruitment and activates caspase-1, which is involved in the cleavage of pro-IL-18 and pro-IL-1β into their active forms.