Severe
trauma renders patients susceptible to
infection. In
sepsis, defective bacterial clearance has been linked to specific deviations in the innate immune response. We hypothesized that innate immune modulations observed during
sepsis also contribute to increased bacterial susceptibility after severe
trauma. A well-established murine model of
burn injury, used to replicate
infection following
trauma, showed that
wound inoculation with P. aeruginosa quickly spreads systemically. The systemic IL-10/
IL-12 axis was skewed after
burn injury with
infection as indicated by a significant elevation in serum
IL-10 and polarization of neutrophils into an anti-inflammatory ("N2"; IL-10(+)
IL-12(-)) phenotype.
Infection with an attenuated P. aeruginosa strain (ΔCyaB) was cleared better than the wildtype strain and was associated with an increased pro-inflammatory neutrophil ("N1"; IL-10(-)
IL-12(+)) response in
burn mice. This suggests that neutrophil polarization influences bacterial clearance after
burn injury. Administration of a TLR5 agonist,
flagellin, after
burn injury restored the neutrophil response towards a N1 phenotype resulting in an increased clearance of wildtype P. aeruginosa after
wound inoculation. This study details specific alterations in innate cell populations after
burn injury that contribute to increased susceptibility to
bacterial infection. In addition, for the first time, it identifies neutrophil polarization as a therapeutic target for the reversal of bacterial susceptibility after injury.