Deficient cytokine expression and neutrophil oxidative burst contribute to impaired cutaneous wound healing in diabetic, biofilm-containing chronic wounds.

Abstract

Diabetic patients exhibit dysregulated inflammatory and immune responses that predispose them to chronic wound infections and the threat of limb loss. The molecular underpinnings responsible for this have not been well elucidated, particularly in the setting of wound biofilms. This study evaluates host responses in biofilm-impaired wounds using the TallyHo mouse, a clinically relevant polygenic model of type 2 diabetes. No differences in cytokine or Toll-like receptor (TLR) expression were noted in unwounded skin or noninoculated wounds of diabetic and wild-type mice. However, diabetic biofilm-containing wounds had significantly less TLR 2, TLR 4, interleukin-1β, and tumor necrosis factor-α expression than wild-type wounds with biofilm (all p < 0.001). Both groups had similar bacterial burden and neutrophil infiltration after development of biofilms at 3 days postwounding, but diabetic wounds had significantly less neutrophil oxidative burst activity. This translated into a log-fold greater bacterial burden and significant delay of wound epithelization for biofilm-impaired diabetic wounds at 10 days postwounding. These results suggest that impaired recognition of bacterial infection via the TLR pathway leading to inadequate cytokine stimulation of antimicrobial host responses may represent a potential mechanism underlying diabetic susceptibility to wound infection and ulceration.

• Authors: Khang T Nguyen, Akhil K Seth, Seok J Hong, Matthew R Geringer, Ping Xie, Kai P Leung, Thomas A Mustoe, Robert D Galiano
• Journal: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Wound Repair Regen) 2013 Nov-Dec Vol. 21 Issue 6 Pg. 833-41 ISSN: 1524-475X [Electronic] United States
• PMID: 24118295 (Publication Type: Journal Article)
• Copyright: © 2013 by the Wound Healing Society.

Chemical References

• Bacterial Proteins
• Interleukin-1beta
• TLR2 protein, human
• TLR4 protein, human
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Bacterial Proteins
• Biofilms
• Chronic Disease
• Diabetes Mellitus, Experimental (microbiology, pathology)
• Gene Expression Regulation, Bacterial
• Interleukin-1beta (metabolism)
• Male
• Mice
• Neutrophils (metabolism)
• Respiratory Burst
• Signal Transduction
• Staphylococcal Infections (physiopathology)
• Staphylococcus aureus (isolation & purification)
• Toll-Like Receptor 2 (metabolism)
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Ulcer (microbiology, pathology)
• Wound Healing
• Wound Infection (microbiology, physiopathology)