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

Wilkinson, T; Dhaliwal, K; Hamilton, T; Lipka, A; Farrell, L; Davidson, D; Duffin, R; Morris, A; Haslett, C; Govan, J; Gregory, C; Sallenave, J; Simpson, A

Journal article

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

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 status:: Published

Peer review status:: Peer reviewed

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APA Style

Wilkinson, T., Dhaliwal, K., Hamilton, T., Lipka, A., Farrell, L., Davidson, D., Duffin, R., Morris, A., Haslett, C., Govan, J., Gregory, C., Sallenave, J., & Simpson, A. (2010). Trappin-2 promotes early clearance of Pseudomonas aeruginosa through CD14-dependent macrophage activation and neutrophil recruitment. American Journal of Pathology, 174(4), 1338–1346.

MLA Style

Wilkinson, T, et al. “Trappin-2 Promotes Early Clearance of Pseudomonas Aeruginosa through CD14-Dependent Macrophage Activation and Neutrophil Recruitment.” American Journal of Pathology, vol. 174, no. 4, 2010, pp. 1338–46.

Chicago Style

Wilkinson, T, K Dhaliwal, T Hamilton, et al. 2010. “Trappin-2 Promotes Early Clearance of Pseudomonas Aeruginosa through CD14-Dependent Macrophage Activation and Neutrophil Recruitment.” American Journal of Pathology 174 (4): 1338–46.
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