Background
Diabetes mellitus is associated with increased tuberculosis risk and severity. We previously reported that tuberculosis susceptibility in diabetic mice
Conclusions
Reduced MARCO and CD14 expression contributes to defective sentinel function of alveolar macrophages, promoting tuberculosis susceptibility in diabetic hosts at a critical early step in the immune response to aerosol infection.
Methods
We tested the capacity of alveolar macrophages from diabetic mice to phagocytose M. tuberculosis ex vivo and promote T-cell activation in vivo.
Results
Alveolar macrophages from diabetic mice had reduced expression of CD14 and macrophage receptor with collagenous structure (MARCO), which recognize the bacterial cell wall component trehalose 6,6'-dimycolate (TDM). Diabetic alveolar macrophages exhibited reduced phagocytosis of M. tuberculosis or TDM-coated latex beads. This alveolar macrophage phenotype was absent in peritoneal and bone marrow-derived macrophages. Transfer of infected alveolar macrophages from diabetic mice into nondiabetic recipients confirmed an intrinsic alveolar macrophage defect that hindered T-cell priming. The diabetic alveolar macrophage phenotype depended in part on expression of the receptor for advanced glycation end products. Conclusions: Reduced MARCO and CD14 expression contributes to defective sentinel function of alveolar macrophages, promoting tuberculosis susceptibility in diabetic hosts at a critical early step in the immune response to aerosol infection.