ABSTRACT
Mycobacterium tuberculosis (M. tb) is a significant intracellular pathogen responsible for numerous infectious disease-related deaths worldwide. It uses ESX-1 T7SS to damage phagosomes and to enter the cytosol of host cells after phagocytosis. During infection, M. tb and host mitochondria release dsDNA, which activates the CGAS-STING1 pathway. This pathway leads to the production of type I interferons and proinflammatory cytokines and activates autophagy, which targets and degrades bacteria within autophagosomes. However, the role of type I IFNs in immunity against M. tb is controversial. While previous research has suggested a protective role, recent findings from cgas-sting1 knockout mouse studies have contradicted this. Additionally, a study using knockout mice and non-human primate models uncovered a new mechanism by which neutrophils recruited to lung infections form neutrophil extracellular traps. Activating plasmacytoid dendritic cells causes them to produce type I IFNs, which interfere with the function of interstitial macrophages and increase the likelihood of tuberculosis. Notably, M. tb uses its virulence proteins to disrupt the CGAS-STING1 signaling pathway leading to enhanced pathogenesis. Investigating the CGAS-STING1 pathway can help develop new ways to fight tuberculosis.
