Format

Send to

Choose Destination
PLoS One. 2014 Jan 15;9(1):e85623. doi: 10.1371/journal.pone.0085623. eCollection 2014.

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

Author information

1
North Carolina Jaycee Burn Center, University of North Carolina, Department of Microbiology and Immunology, Chapel Hill, North Carolina, United States of America.
2
North Carolina Jaycee Burn Center, University of North Carolina, Department of Surgery, Chapel Hill, North Carolina, United States of America.
3
University of Arizona, Department of Immunobiology, Tucson, Arizona, United States of America.
4
University of North Carolina, Department of Microbiology and Immunology, Chapel Hill, North Carolina, United States of America.
5
North Carolina Jaycee Burn Center, University of North Carolina, Department of Microbiology and Immunology, Chapel Hill, North Carolina, United States of America ; North Carolina Jaycee Burn Center, University of North Carolina, Department of Surgery, Chapel Hill, North Carolina, United States of America.

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 (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.

PMID:
24454904
PMCID:
PMC3893295
DOI:
10.1371/journal.pone.0085623
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center