Single-cell profiling of the lung immune cells of diabetes-tuberculosis comorbidity reveals reduced type-II interferon and elevated Th17 responses.

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.