The pathway of autophagy in the epigenetic landscape of <i>Mycobacterium</i>-host interactions

Macroautophagy (autophagy) is an evolutionarily conserved process that degrades excess cytoplasmic components, such as protein aggregates and damaged organelles, by encapsulating them within double-membrane autophagosomes. These autophagosomes undergo distinct stages – initiation, phagophore nucleation, expansion, and closure – before fusing with lysosomes (or occasionally endosomes) for degradation and recycling. This process is regulated by ATG (autophagy related) proteins, which govern autophagosome formation and lysosomal fusion. Epigenetic modifications and transcription factors can regulate <i>ATG</i> gene expression in the nucleus. Autophagy also plays a key role in eliminating intracellular <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) through the lytic and antimicrobial activities of autolysosomes, which are more potent antimicrobial compartments than conventional phagosomes. Emerging evidence suggests that <i>Mtb</i> can modify the host epigenome and transcriptional machinery, significantly affecting the host immune response. This review explores the epigenetic regulation of autophagy during mycobacterium-host interactions. The interplay between epigenetic regulation and autophagy highlights a crucial aspect of host-pathogen interactions during <i>Mtb</i> infection. Understanding how <i>Mtb</i> manipulates the host epigenome to regulate autophagy could lead to the development of novel therapeutic strategies that enhance autophagic pathways or counteract <i>Mtb’s</i> immune evasion tactics.