Diabetes-Tuberculosis Comorbidity Characterized by Reduced Type-II Interferon and Elevated Th17 Responses
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Understanding the perturbed lung immune cell distribution and their functionality in tuberculosis is well documented; however, limited reports covered their disruption, if any, in diabetes-tuberculosis (DM-TB) comorbid conditions. Here, we measured serum cytokines and employed single-cell RNA-seq to investigate the molecular mechanisms that govern the heterogeneity in host immune response in DM- TB comorbid conditions. Diabetes associated with chronic hyperinflammation and reduced lung- infiltrating immune cells delayed 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 observed in DM-TB. This study highlights chronic inflammation, hyperglycemia, and dyslipidemia associated with diabetes impairing anti-TB immunity, and selective inhibition of aberrant IL-16 secretion and Th17 cell activation might provide strategies for better management of this comorbidity.
Highlights
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Elevated serum IL-6, TNF-α, and IL-17A levels reflect hyperinflammation in diabetic mice.
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Lung CD3+ and CD11c+ cell single-cell RNA-seq profiles reveals inflammaging in diabetic mice.
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Fewer lung-infiltrating CD3+ cells in diabetes-tuberculosis (DM-TB) mice suggested delayed immune response.
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Weaker pro-inflammatory response, with reduced Th1/CD4-CTL activity and more Th17-driven tissue damage observed in DM-TB mice.
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