Type 2 diabetes impairs macrophage antimicrobial capability and increases susceptibility to sepsis.

Abstract

Sepsis remains one of the primary causes of mortality in intensive care units, with an overall death rate of approximately 20%. Type 2 diabetes (T2D) exacerbates the incidence of infections, leading to increased long-term morbidity and mortality associated with sepsis. Macrophages are critical for the defense and clearance of invading pathogens during sepsis. Nevertheless, limited research has addressed the impact of T2D on macrophage dysfunction in sepsis conditions. In this study, we observed a significant impairment in the phagocytic and intracellular bacterial killing abilities of macrophages in a T2D sepsis model. Utilizing the cecal ligation and puncture sepsis model, we revealed a reduction in tissue-resident macrophages and an elevated bacterial burden in T2D mice. Moreover, peripheral monocytes from T2D patients and peritoneal macrophages from T2D mice exhibited the dampened phagocytic and intracellular killing abilities, characterized by decreased expressions of phagocytic receptors and a diminished capacity to generate reactive oxygen species. In addition, exogenous granulocyte-macrophage colony-stimulating factor administration enhanced survival rates and reduced bacterial loads in T2D mice by restoring phagocytosis and bacterial eradication of macrophages/monocytes. Collectively, these data suggest that T2D contributes to macrophage dysfunction and impaired bacterial clearance, leading to an increased susceptibility to sepsis.