Post-traumatic pulmonary infection: the innate immune response protects the lung at the expense of the healing cutaneous wound

Autor: Meredith Crane, Yun Xu, Sean F. Monaghan, Benjamin M. Hall, Holly L. Tran, William L Henry, Jorge E. Albina, Amanda M. Jamieson
Rok vydání: 2019
Předmět:
Zdroj: The Journal of Immunology. 202:62.10-62.10
ISSN: 1550-6606
0022-1767
Popis: Hospitalized trauma patients have an increased risk of pulmonary infection. The acute response to injury, which relies on the coordinated activity of recruited leukocytes, may affect the early, innate immune-mediated control of lung infection. We hypothesized that a cutaneous wound would inhibit the ability of innate leukocytes to respond to a subsequent pulmonary bacterial infection. To address this, we developed a murine model of post-injury pneumonia. Mice were wounded by the dorsal subcutaneous implantation of polyvinyl alcohol sponges, which models the acute stages of wound repair, and a cohort was infected intranasally with the opportunistic bacterium Klebsiella oxytoca. For comparison, a control group was only infected. Wounding did not alter the early control of lung bacterial infection, the infiltration of innate leukocytes into the infected lung, or cytokine and chemokine levels in the bronchoalveolar lavage fluid. In contrast, pulmonary infection suppressed wound healing, caused decreased monocyte and neutrophil trafficking and lower cytokine and chemokine concentrations in the wound. Exogenous delivery of CCL2 and CXCL1 to the wound increased the number of neutrophils and accelerated healing. However, this led to increased pulmonary bacterial burden, highlighting the balance of cellular responses required to protect the lung. These data suggest that the innate immune system prioritizes the protection of one site above the other when faced with competing inflammatory insults. Here, early control of lung infection took priority over the healing wound. This work aims to elucidate mechanisms by which the innate immune system responds to multiple insults, which may be broadly applicable to inflammatory conditions.
Databáze: OpenAIRE