Curcumin enhances mycobacterial clearance in diabetes-tuberculosis by targeting the WNT6.

BACKGROUND: The convergence of tuberculosis (TB) and diabetes mellitus (DM) represents a critical global health challenge. Chronic hyperglycemia compromises macrophage bactericidal capacity, leading to excessive reactive oxygen species (ROS) accumulation and proinflammatory microenvironment that causing pathological damage to the lungs and paradoxically favors Mtb survival. OBJECTIVE: This study aimed to investigate the therapeutic potential of curcumin in mitigating metabolic-immune dysfunction in DM-TB comorbidity via WNT6-mediated macrophage modulation. METHODS: This study established a Type 2 Diabetes (T2D) mouse model using C57BL/6 mice, Mice were infected with H37Rv via inhalation, followed by curcumin administration. Various methodologies were employed, including RNA sequencing, flow cytometry, seahorse and Confocal Microscopy. THP-1 cells and bone marrow-derived macrophages (BMDMs) were differentiated and used for infection studies, assessing cell viability and intracellular bacterial burden. RESULTS: Curcumin effectively reversed the pathological alterations associated with hyperglycemia. Specifically, it suppressed WNT6 expression, reduced lipid droplet formation, and decreased FAO in macrophages. Additionally, curcumin mitigated oxidative stress, restored immune homeostasis, and enhanced Mtb clearance. CONCLUSION: Curcumin emerged as a viable intervention for strengthening host defense against TB in diabetic populations.