Murine burn lesion model for studying acute and chronic wound infections
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Murine burn lesion model for studying acute and chronic wound infections. / Calum, Henrik; Trøstrup, Hannah; Laulund, Anne Sofie; Thomsen, Kim; Christophersen, Lars; Høiby, Niels; Moser, Claus.
In: APMIS, Vol. 130, No. 7, 2022, p. 477-490.Research output: Contribution to journal › Review › peer-review
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TY - JOUR
T1 - Murine burn lesion model for studying acute and chronic wound infections
AU - Calum, Henrik
AU - Trøstrup, Hannah
AU - Laulund, Anne Sofie
AU - Thomsen, Kim
AU - Christophersen, Lars
AU - Høiby, Niels
AU - Moser, Claus
N1 - Publisher Copyright: © 2022 Scandinavian Societies for Medical Microbiology and Pathology.
PY - 2022
Y1 - 2022
N2 - Acute wounds, such as thermal injury, and chronic wounds are challenging for patients and the healthcare system around the world. Thermal injury of considerable size induces immunosuppression, which renders the patient susceptible to wound infections, but also in other foci like the airways and urinary tract. Infected thermal lesions can progress to chronic wounds with biofilm making them more difficult to treat. While animal models have their limitations, murine wound models are still the best tool at the moment to identify strategies to overcome these challenges. Here, we present a murine burn model, which has been developed to study biofilm formation, the significance of wound healing, and for identifying novel treatment candidates. Investigating the effect of a thermal injury in mice, we observed that 48 h after introduction of the injury, the mice showed a reduction in polymorphonuclear neutrophil granulocytes (PMNs) and a reduced capacity for phagocytosis and oxidative burst. Regarding the chronic wound, Pseudomonas aeruginosa biofilm arrested wound healing and kept the wound in an inflammatory state, but suppressing PMN function by means of the PMN factor S100A8/A9, corresponding to observations in human venous leg ulcers. Monotherapy and dual treatment with S100A8/A9 and ciprofloxacin on P. aeruginosa biofilm-infected murine wounds have been investigated. In combination, S100A8/A9 and ciprofloxacin reduced the bacterial quantity, lowered the proinflammatory response, and increased anti-inflammatory cytokines after 4 days of treatment. When the treatment was prolonged, an additional prevention of resistance development was detected in all the dual-treated mice. In the present review, we provide data on using the murine model for research with the aim of better understanding pathophysiology of wounds and for identifying novel treatments for humans suffering from these lesions.
AB - Acute wounds, such as thermal injury, and chronic wounds are challenging for patients and the healthcare system around the world. Thermal injury of considerable size induces immunosuppression, which renders the patient susceptible to wound infections, but also in other foci like the airways and urinary tract. Infected thermal lesions can progress to chronic wounds with biofilm making them more difficult to treat. While animal models have their limitations, murine wound models are still the best tool at the moment to identify strategies to overcome these challenges. Here, we present a murine burn model, which has been developed to study biofilm formation, the significance of wound healing, and for identifying novel treatment candidates. Investigating the effect of a thermal injury in mice, we observed that 48 h after introduction of the injury, the mice showed a reduction in polymorphonuclear neutrophil granulocytes (PMNs) and a reduced capacity for phagocytosis and oxidative burst. Regarding the chronic wound, Pseudomonas aeruginosa biofilm arrested wound healing and kept the wound in an inflammatory state, but suppressing PMN function by means of the PMN factor S100A8/A9, corresponding to observations in human venous leg ulcers. Monotherapy and dual treatment with S100A8/A9 and ciprofloxacin on P. aeruginosa biofilm-infected murine wounds have been investigated. In combination, S100A8/A9 and ciprofloxacin reduced the bacterial quantity, lowered the proinflammatory response, and increased anti-inflammatory cytokines after 4 days of treatment. When the treatment was prolonged, an additional prevention of resistance development was detected in all the dual-treated mice. In the present review, we provide data on using the murine model for research with the aim of better understanding pathophysiology of wounds and for identifying novel treatments for humans suffering from these lesions.
KW - animal model
KW - burn wound
KW - chronic wound biofilm
KW - healing
KW - host response
KW - immune system
KW - Pseudomonas aeruginosa
U2 - 10.1111/apm.13228
DO - 10.1111/apm.13228
M3 - Review
C2 - 35441434
AN - SCOPUS:85132645731
VL - 130
SP - 477
EP - 490
JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
SN - 0903-4641
IS - 7
ER -
ID: 313377532