biostudies-literatureShariq MDepartment of Biotechnology, Ministry of Science and Technology, India636644https://www.ebi.ac.uk/biostudies/studies/S-EPMC7969667biostudies-literatureUnknown12Reductive evolution has endowed <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) with moonlighting in protein functions. We demonstrate that RipA (Rv1477), a peptidoglycan hydrolase, activates the NFκB signaling pathway and elicits the production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-12, through the activation of an innate immune-receptor, toll-like receptor (TLR)4. RipA also induces an enhanced expression of macrophage activation markers MHC-II, CD80, and CD86, suggestive of M1 polarization. RipA harbors LC3 (Microtubule-associated protein 1A/1B-light chain 3) motifs known to be involved in autophagy regulation and indeed alters the levels of autophagy markers LC3BII and P62/SQSTM1 (Sequestosome-1), along with an increase in the ratio of P62/Beclin1, a hallmark of autophagy iFrontiers in immunology<i>Mycobacterium tuberculosis</i> RipA Dampens TLR4-Mediated Host Protective Response Using a Multi-Pronged Approach Involving Autophagy, Apoptosis, Metabolic Repurposing, and Immune Modulation.PMC7969667BT/PR23099/NER/95/632/2017BT/PR12817/COE/34/23/2015Sharma NSheikh JASingh JEhtesham NZHasnain SEShariq MQuadir NKhubaib Mfalse<i>Mycobacterium tuberculosis</i> RipA Dampens TLR4-Mediated Host Protective Response Using a Multi-Pronged Approach Involving Autophagy, Apoptosis, Metabolic Repurposing, and Immune Modulation.Reductive evolution has endowed <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) with moonlighting in protein functions. We demonstrate that RipA (Rv1477), a peptidoglycan hydrolase, activates the NFκB signaling pathway and elicits the production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-12, through the activation of an innate immune-receptor, toll-like receptor (TLR)4. RipA also induces an enhanced expression of macrophage activation markers MHC-II, CD80, and CD86, suggestive of M1 polarization. RipA harbors LC3 (Microtubule-associated protein 1A/1B-light chain 3) motifs known to be involved in autophagy regulation and indeed alters the levels of autophagy markers LC3BII and P62/SQSTM1 (Sequestosome-1), along with an increase in the ratio of P62/Beclin1, a hallmark of autophagy i2021-01-01T00:00:00Z20212026-05-07T03:19:44.918Z2025-04-03T21:33:12.041ZS-EPMC79696673374697610.3389/fimmu.2021.636644