Article
Reduced neutrophil apoptosis in diabetic mice during Staphylococcus aureus infection leads to prolonged TNFalpha production and reduced neutrophil clearance
Verringerte Apoptose neutrophiler Granulozyten im Rahmen einer Infektion mit Staphylococcus aureus bei diabetischen Mäusen
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Authors
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F. Hanses
- Klinik und Poliklinik für Innere Medizin I, Infektiologie, Regensburg, Germany; Channing Laboratory, Harvard Medical School, Boston, United States
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J. C. Lee
- Channing Laboratory, Harvard Medical School, Boston, United States
| Published: | June 2, 2010 |
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Outline
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Objectives: Diabetic patients frequently suffer from chronic infections and inflammation. At the same time, diabetes mellitus is a common comorbidity in Staphylococcus aureus infections associated with a poorer outcome. Our goal was to study the role of neutrophils in S. aureus infections complicated by diabetes.
Methods: We used age-matched diabetic and non-diabetic NOD mice challenged with S. aureus i.p. as an animal model of systemic infection to study neutrophil apoptosis during infection (as measured by nuclear condensation, Annexin binding and TUNEL staining). Fluorescent labeled neutrophils were used to investigate neutrophil clearance by macrophages and intracellular cytokine staining to study the production of proinflammatory cytokines.
Results: Neutrophils isolated from diabetic mice infected with S. aureus displayed enhanced viability and a 11–35% lower rate of apoptosis in all assays used. Similarly, neutrophils from diabetic mice stimulated with S. aureus in vitro underwent apoptosis to a lower degree compared to non-diabetic controls whereas spontaneous induction of apoptosis was not significantly altered. These differences were dependant on the presence of S. aureus and a functional respiratory burst. Reduced apoptosis lead to a decreased uptake of neutrophils by macrophages (8.4% versus 13.4% of all macrophages with ingested neutrophils) and neutrophils from diabetic mice continued to produce significantly more TNFalpha (43.2% versus 23.8% of all neutrophils positive for TNFalpha after 10h).
Conclusions: Decreased pathogen induced neutrophil apoptosis may contribute to a prolonged inflammatory reaction to infection with S. aureus in diabetic hosts.
