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Deficient cytokine expression and neutrophil oxidative burst contribute to impaired cutaneous wound healing in diabetic, biofilm‐containing chronic wounds
Author(s) -
Nguyen Khang T.,
Seth Akhil K.,
Hong Seok J.,
Geringer Matthew R.,
Xie Ping,
Leung Kai P.,
Mustoe Thomas A.,
Galiano Robert D.
Publication year - 2013
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12109
Subject(s) - biofilm , cytokine , respiratory burst , medicine , wound healing , immunology , oxidative stress , microbiology and biotechnology , inflammation , immune system , diabetes mellitus , tumor necrosis factor alpha , proinflammatory cytokine , innate immune system , biology , bacteria , endocrinology , genetics
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 T ally H o 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.