Epigenetic modulation in tuberculosis – mycobacterial defense mechanism to host immune responses

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Epigenetic regulators alter chromatin to control transcription in response to pathogens. Histone acetylation influences DNA accessibility and gene expression, impacting latent and active tuberculosis (TB). Mycobacterium tuberculosis (MTB) requires specific components to harm the host immune system. The review aims to analyze MTB epigenetic processes and the impact of host immune system genes. This review analyzed histone deacetylases, DNA methyltransferases, epigenetic linkages to non-coding RNAs, and enhanced epigenetic detection. Also, it described mycobacteria’s evasion of the host immune system through lipid metabolism, autophagy, oxidative stress, and epigenetic efflux pump inhibitors. The MTB DNA methyltransferase (DNMT) Rv2966c (I6XFS7) modifies histones H3 and H4, impacting host transcription. The MTB acetyltransferase EIS ( Rv2416c , P9WFK7) enhances human IL-10 synthesis and acetylates the H3 gene promoter. MTB infection activates an epigenetic repressor complex with HDAC1 and ZBTB25, which restricts IL-12B production in macrophages. MTB inhibits HDAC1 and ZBTB25, enhances autophagic clearance, reduces bacterial viability, and increases IL-12B. ADP-ribosyl polymerase Rv1899c interacts with HDAC1 and may inhibit immune activation. Rv1899c interacts with HDAC1 and ZBTB25 to silence inflammatory promoters and maintain immune suppression without effector release. NLRP3 activation is influenced by DNA methylation. DNMT inhibitor DAC increased transcriptional activity in vitro , while DNA methylase Sss I decreased NLRP3 promoter activity. In small RNAs, links to epigenetics, the miR-15/16 family’s miR-15a-5p , regulate apoptosis, the cell cycle, and inflammatory cytokines. MiR-15a-5p affects inflammation by targeting genes in the BCL2, IKKα, and NF-κB pathways. Thus, epigenetic studies on MTB are vital to identify host immune evasion and host-directed therapy.