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bioRxiv · 10.1101/2024.10.24.619799

Diabetes-Tuberculosis Comorbidity Characterized by Reduced Type-II Interferon and Elevated Th17 Responses.

Chaudhary, S.·Sravya, M.·Pahwa, F.·V, S.·Singh, P.·Chaturvedi, S.·Mohanty, D.·Dash, D.·Nanda, R.
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Abstract

Understanding the perturbed lung immune cells distribution and its functionality in tuberculosis (TB) is well documented; however, limited reports have covered their disruption, if any, in diabetes-tuberculosis (DM-TB) comorbid conditions. Here, we employed single-cell RNA-seq to investigate the molecular mechanisms that govern the heterogeneity in host immune response in DM-TB comorbid conditions. Diabetes is associated with chronic hyperinflammation and reduced lung-infiltrating immune cells, which delays the immune response to Mycobacterial infection. scRNA-seq of lung CD3 and CD11c cells revealed compromised adaptive and innate immunity, with decreased Th1 and M1 macrophage populations in DM-TB mice. A dampened immune response, marked by increased IL-16 signaling and reduced TNF and IFN-II responses, was observed in DM-TB. This study highlights chronic inflammation, hyperglycemia, and dyslipidemia associated with diabetes impairing anti-TB immunity. Selective inhibition of aberrant IL-16 secretion and Th17 cell activation might provide strategies for better managing DM-TB comorbidity.

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Chaudhary, S., Sravya, M., Pahwa, F., V, S., Singh, P., Chaturvedi, S., Mohanty, D., Dash, D., Nanda, R.. 2024-10-28. Diabetes-Tuberculosis Comorbidity Characterized by Reduced Type-II Interferon and Elevated Th17 Responses.. https://doi.org/10.1101/2024.10.24.619799

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