IntroductionThe dual epidemic of tuberculosis (TB) and type 2 diabetes mellitus (T2DM) presents a critical global health challenge, as diabetic immunosuppression increases TB susceptibility while TB infection exacerbates glucose intolerance. Because nuclear receptors (NRs) regulate both metabolic pathways and infectious disease responses, they represent promising therapeutic targets.
This study aimed to evaluate the therapeutic potential of targeting overlapping NRs to manage TB-T2DM comorbidity.MethodsA comorbid mouse model was established by inducing T2DM via a high-fat diet and streptozotocin, followed by an aerosol challenge with Mycobacterium tuberculosis (M. tb).
Mice were categorized into three groups: uninfected controls, M. tb-infected non-diabetic, and M.
tb-infected diabetic mice. NR expression profiling was performed on alveolar macrophages, specifically screening endocrine, adopted orphan, and orphan NRs.
Based on this profile, comorbid mice were treated with a combination therapy (CT) consisting of specific ligands for the most promising NR targets Vdr, Lxr and Rev-erbα.ResultsExpression screening identified Vdr, Rev-erbα, and Lxr as key dysregulated receptors with dual roles in TB and T2DM pathogenesis.
Frontiers in Immunology published a clinical update in Infectious Disease on 10 Jun 2026.
The item focuses on Integrated approaches to target nuclear receptors for managing the co-morbidity of tuberculosis and diabetes.
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