Pulmonary infection interrupts acute cutaneous wound healing through disruption of chemokine signals

Abstract

Abstract Individuals who are hospitalized with traumatic injuries are susceptible to nosocomial pneumonia. While the effect of the injury on pulmonary infection has been examined in many contexts, it is less well understood how lung infection affects healing wounds. To address this, we examined the outcomes of laparotomized patients with and without pneumonia using the American College of Surgeons NSQIP database. Individuals who developed pneumonia were twice as likely to experience wound dehiscence compared to those without pneumonia. We hypothesized that the immune response could not to meet the demands of competing inflammatory insults in the skin and lungs. To examine this, we developed murine models of post-operative lung infection. Mice were wounded by the dorsal subcutaneous implantation of polyvinyl alcohol (PVA) sponges or tail skin excision, then infected intranasally with Klebsiella oxytoca. PVA sponge wounds allow for the examination of cellular and cytokine responses during acute wound healing, while wound closure can be measured with the tail skin excision model. Pulmonary infection led to rapid suppression of wound IL-1α, IL-1β, and chemokines. This was followed by decreased accumulation of innate leukocytes in the wound and delayed wound closure. In contrast, lung antibacterial responses were not affected by the presence of surgical wounds. Wound healing in infected mice could be rescued by the addition of the chemokines CCL2 and CXCL1; however, this treatment caused a delay in bacterial clearance in the lungs. These data suggest that the immune response is not fully equipped to respond to disparate and competing inflammatory insults, which could have implications beyond the setting of post-operative pneumonia.