Depletion of

Objectives: Methods: The structure of Rv3737 was predicted using bioinformatics tools. Macrophage polarization markers were assessed by real-time PCR for M1/M2-associated cytokines, and flow cytometry for CD86 Results: Rv3737 is predicted to contain 10 transmembrane segments enriched in aliphatic amino acids. Deletion of Rv3737 in H37Rv (H37RvΔRv3737) led to upregulation of M1 markers (TNF-α, IL-1β, IL-6, iNOS, MCP-1, CD86) and downregulation of M2 markers (Arg-1, IL-10, TGF-β, CD206). Conversely, overexpression of Rv3737 (MS_Rv3737) promoted M2 polarization. RNA sequencing indicated NF-κB pathway activation in macrophages infected with H37RvΔRv3737, along with increased phosphorylation of P65, IκB, ERK, and P38. Inhibition of NF-κB (with JSH-23) and P38 MAPK (with SB203580) reduced iNOS levels and partially restored Mtb survival, indicating that Rv3737 deletion enhances the macrophage antimicrobial response. Conclusions: Rv3737 suppresses M1 macrophage polarization to promote Mtb survival. Its deletion enhances host antimicrobial activity by activating NF-κB and MAPK signaling pathways. Targeting Rv3737 may represent a novel strategy for tuberculosis therapy.