Pulmonary infection interrupts acute cutaneous wound healing through disruption of chemokine signals
SummaryStudies of the immune response typically focus on single-insult systems, with little known about how multi-insult encounters are managed. Pneumonia in patients recovering from surgery is a clinical situation that exemplifies the need for the patient to mount two distinct immune responses. Examining this, we have determined that poor wound healing is an unreported complication of pneumonia in laparotomy patients. Using mouse models, we found that lung infection suppressed the trafficking of innate leukocytes to wounded skin, while pulmonary resistance to the bacterial infection was maintained. The dual insults caused distinct systemic and local changes to the inflammatory response, the most striking being a rapid and sustained decrease in chemokine levels at the wound site of mice with pneumonia. Remarkably, replenishing wound chemokine levels completely rescued the wound-healing rate in mice with a pulmonary infection. These findings have broad implications for understanding the mechanisms guiding the innate immune system to prioritize inflammatory sites.One Sentence SummaryChemokine-mediated signaling drives the prioritization of innate immune responses to bacterial pulmonary infection over cutaneous wound healing.HighlightsHuman laparotomy patients with pneumonia have an increased rate of incision dehiscence, and this observation can be recapitulated in mouse models of bacterial lung infections and skin wounds.Lung infection causes rapid and sustained suppression of skin wound chemokine and inflammatory cytokine production as well as leukocyte recruitment.Unique systemic shifts in the immune compartment occur with two inflammatory insults, including the cytokine/chemokine signature and the mobilization, recruitment, and phenotype of innate leukocytes.Restoration of chemokine signaling in the wounds of mice that have a lung infection results in increased neutrophil trafficking to the wound site and rescues the rate of healing.Graphical Abstract
