Trappin-2 promotes early clearance of Pseudomonas aeruginosa through CD14-dependent macrophage activation and neutrophil recruitment

Thomas S Wilkinson, Kevin Dhaliwal, Thomas W Hamilton, Alexander F Lipka, Lesley Farrell, Donald J Davidson, Rodger Duffin, Andrew Conway Morris, Chris Haslett, John R W Govan, Christopher D Gregory, Jean-Michel Sallenave, A John Simpson

Research output: Contribution to journalArticlepeer-review

Abstract

Microaspiration of Pseudomonas aeruginosa contributes to the pathogenesis of nosocomial pneumonia. Trappin-2 is a host defense peptide that assists with the clearance of P. aeruginosa through undefined mechanisms. A model of macrophage interactions with replicating P. aeruginosa (strain PA01) in serum-free conditions was developed, and the influence of subantimicrobial concentrations of trappin-2 was subsequently studied. PA01 that was pre-incubated with trappin-2 (at concentrations that have no direct antimicrobial effects), but not control PA01, was cleared by alveolar and bone marrow-derived macrophages. However, trappin-2-enhanced clearance of PA01 was completely abrogated by CD14- null macrophages. Fluorescence microscopy demonstrated the presence of trappin-2 on the bacterial cell surface of trappin-2-treated PA01. In a murine model of early lung infection, trappin-2-treated PA01 was cleared more efficiently than control PA01 2 hours of intratracheal instillation. Furthermore, trappin-2-treated PA01 up-regulated the murine chemokine CXCL1/KC after 2 hours with a corresponding increase in neutrophil recruitment 1 hour later. These in vivo trappin-2-treated PA01 effects were absent in CD14-deficient mice. Trappin-2 appears to opsonize P. aeruginosa for more efficient, CD14-dependent clearance by macrophages and contributes to the induction of chemokines that promote neutrophil recruitment. Trappin-2 may therefore play an important role in innate recognition and clearance of pathogens during the very earliest stages of pulmonary infection.
Original languageEnglish
Pages (from-to)1338-1346
Number of pages9
JournalAmerican Journal of Pathology
Volume174
Issue number4
DOIs
Publication statusPublished - Apr 2009

Fingerprint Dive into the research topics of 'Trappin-2 promotes early clearance of Pseudomonas aeruginosa through CD14-dependent macrophage activation and neutrophil recruitment'. Together they form a unique fingerprint.

Cite this