Triaging the innate immune system: Responding to lung infections suppresses the dermal wound healing response

Abstract

Abstract The development of pneumonia is a risk for hospitalized patients. Retrospective analysis of patient data revealed a strong correlation with the development of pneumonia and poor wound healing. Responding to lung infections and the healing wound response involve many of the same innate immune cell types, in particular macrophages, monocytes, and neutrophils. This study addresses the impact of lung infections on the ability to heal a dermal wound at a distal site. Using two in vivo models of injury combined with either bacterial (Klebsiella or Streptococcus) or viral (IAV) lung infections, this study unequivocally demonstrates that lung infections suppress the ability to heal wounds. Cutaneous wound healing is delayed in mice that have an ongoing lung infection. There is a decrease in trafficking of innate immune cells, in particular neutrophils and monocytes, into wounds of mice that have an ongoing lung infection. There are also decreased chemokines and cytokines in wounds from infected mice. Systemic changes of the innate immune system occur after wounding and infection that impact immune cell trafficking into wounds, but allow the immune response in the lung to remain intact. There are also alterations in the wound environment when there are simultaneous wounds and lung infections. By redirecting the innate immune response to the wounds we are able to increase wound healing. This information will allow for the better monitoring and supportive care for patients with this type of complex disease sequelae.