Flagellin treatment prevents increased susceptibility to systemic bacterial infection after injury by inhibiting anti-inflammatory IL-10+ IL-12- neutrophil polarization

Crystal J. Neely, Laurel B. Kartchner, April E. Mendoza, Brandon M. Linz, Jeffrey A. Frelinger, Matthew C. Wolfgang, Robert Maile, Bruce A. Cairns

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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 (DCyaB) was cleared better than the wildtype strain and was associated with an increased proinflammatory neutrophil (''N1''; IL-10 2IL-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.

Original languageEnglish (US)
Article numbere85623
JournalPloS one
Volume9
Issue number1
DOIs
StatePublished - Jan 15 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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