Abstract
Diabetes is a frequent underlying medical condition among individuals with Staphylococcus aureus infections, and diabetic patients often suffer from chronic inflammation and prolonged infections. Neutrophils are the most abundant inflammatory cells during the early stages of bacterial diseases, and previous studies have reported deficiencies in neutrophil function in diabetic hosts. We challenged age-matched hyperglycemic and normoglycemic NOD mice intraperitoneally with S. aureus and evaluated the fate of neutrophils recruited to the peritoneal cavity. Neutrophils were more abundant in the peritoneal fluids of infected diabetic mice by 48 h after bacterial inoculation, and they showed prolonged viability ex vivo compared to neutrophils from infected nondiabetic mice. These differences correlated with reduced apoptosis of neutrophils from diabetic mice and were dependent upon the presence of S. aureus and a functional neutrophil respiratory burst. Decreased apoptosis correlated with impaired clearance of neutrophils by macrophages both in vitro and in vivo and prolonged production of proinflammatory tumor necrosis factor alpha by neutrophils from diabetic mice. Our results suggest that defects in neutrophil apoptosis may contribute to the chronic inflammation and the inability to clear staphylococcal infections observed in diabetic patients.
Highlights
Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia
We observed delayed neutrophil recruitment to the site of infection in the diabetic mice, and this finding was consistent with chemokine levels in the infected hindpaw tissues of the diabetic mice that were significantly lower than those of agematched nondiabetic littermates [17]
Ketoacidosis in patients with type 1 diabetes is frequently precipitated by infections [25], and diabetic patients in general are more susceptible to a variety of infections [26,27], especially those caused by S. aureus
Summary
Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia. Patients with type 1 diabetes fail to produce insulin, and patients with type 2 diabetes develop resistance to insulin. Diabetic foot infections are a major complication of diabetes mellitus [4], and chronic leg ulcers are a frequent cause for hospitalizations and amputations among diabetic patients. Whereas some authors report impaired bactericidal function and decreased phagocytic activity by neutrophils from diabetic patients [12,13], others have failed to demonstrate significant differences in neutrophil function in diabetic versus control patients [14]. Some of these conflicting findings may be explained by heterogeneous patient populations. Animal models of diabetes offer the advantage of examining the function and fate of neutrophils in defined models of infections [15,16,17]
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