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Trappin-2 promotes early clearance of pseudomonas aeruginosa through CD14-dependent macrophage activiation and neutrophil recruitment

Lookup NU author(s): Professor John Simpson

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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.


Publication metadata

Author(s): Wilkinson TS, Dhaliwal K, Hamilton TW, Lipka AF, Farrell L, Davidson DJ, Duffin R, Haslett C, Govan JRW, Gregory CD, Sallenave JM, Simpson AJ

Publication type: Article

Publication status: Published

Journal: American Journal of Pathology

Year: 2009

Volume: 174

Issue: 4

Pages: 1338-1346

Print publication date: 09/12/2010

ISSN (print): 0002-9440

ISSN (electronic): 1525-2191

Publisher: American Society for Investigative Pathology

URL: http://dx.doi.org/10.2353/ajpath.2009.080746

DOI: 10.2353/ajpath.2009.080746


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