Chronic Pseudomonas aeruginosa biofilm infection impairs murine S100A8/A9 and neutrophil effector cytokines—implications for delayed wound closure?

TY - JOUR

T1 - Chronic Pseudomonas aeruginosa biofilm infection impairs murine S100A8/A9 and neutrophil effector cytokines—implications for delayed wound closure?

AU - Trøstrup, Hannah

AU - Lerche, Christian Johann

AU - Christophersen, Lars Jackie

AU - Thomsen, Kim

AU - Jensen, Peter Østrup

AU - Hougen, Hans Petter

AU - Høiby, Niels

AU - Moser, Claus

N1 - Erratum: https://doi.org/10.1093/femspd/ftx110

PY - 2017/10/1

Y1 - 2017/10/1

N2 - The impact of Pseudomonas aeruginosa biofilm infections in chronic wounds and clinical implication for healing is receiving increased attention. However, the pathophysiology of host/pathogen interplay is not fully understood. By further revealing the mechanisms, necessary new treatment strategies may be identified. Since the background for chronic wounds is diverse, representative animal models are important. We assessed host response and spontaneous wound closure in the relatively resistant C3H/HeN and the susceptible BALB/c mouse strain. Full-thickness burn wounds were inflicted in 108 mice. Pseudomonas aeruginosa biofilm (106 colony forming units) was injected subcutaneously in 72 mice, euthanised day 4, 7 or 10 days post-infection. Wounds were analysed for neutrophil host response markers: S100A8/A9, keratinocyte-derived chemokine and granulocyte-colony stimulating factor. Total peripheral blood leucocyte and polymorphonuclear count were assessed in parallel. Histopathology evaluated wound inflammatory burden. Photoplanimetry described macroscopical wound closure. Stable chronic wound infection was established in all challenged mice. Pseudomonas aeruginosa biofilm suppressed neutrophil host response in wounds. C3H/HeN mice achieved earlier systemic inflammatory control and healed faster than BALB/c mice. Pseudomonas aeruginosa biofilms perturb host defence thereby inducing a steady state of chronic infection which may impair wound healing. These results indicate therapeutic options for immune modulation of biofilm-infected wounds.

AB - The impact of Pseudomonas aeruginosa biofilm infections in chronic wounds and clinical implication for healing is receiving increased attention. However, the pathophysiology of host/pathogen interplay is not fully understood. By further revealing the mechanisms, necessary new treatment strategies may be identified. Since the background for chronic wounds is diverse, representative animal models are important. We assessed host response and spontaneous wound closure in the relatively resistant C3H/HeN and the susceptible BALB/c mouse strain. Full-thickness burn wounds were inflicted in 108 mice. Pseudomonas aeruginosa biofilm (106 colony forming units) was injected subcutaneously in 72 mice, euthanised day 4, 7 or 10 days post-infection. Wounds were analysed for neutrophil host response markers: S100A8/A9, keratinocyte-derived chemokine and granulocyte-colony stimulating factor. Total peripheral blood leucocyte and polymorphonuclear count were assessed in parallel. Histopathology evaluated wound inflammatory burden. Photoplanimetry described macroscopical wound closure. Stable chronic wound infection was established in all challenged mice. Pseudomonas aeruginosa biofilm suppressed neutrophil host response in wounds. C3H/HeN mice achieved earlier systemic inflammatory control and healed faster than BALB/c mice. Pseudomonas aeruginosa biofilms perturb host defence thereby inducing a steady state of chronic infection which may impair wound healing. These results indicate therapeutic options for immune modulation of biofilm-infected wounds.

U2 - 10.1093/femspd/ftx068

DO - 10.1093/femspd/ftx068

M3 - Journal article

C2 - 28645160

SN - 2049-632X

VL - 75

JO - Pathogens and Disease

JF - Pathogens and Disease

IS - 7

M1 - ftx068

ER -