IFN regulatory factor 3 contributes to the host response during Pseudomonas aeruginosa lung infection in mice

Svetlana O. Carrigan, Robert Junkins, Yong Jun Yang, Adam MacNeil, Christopher Richardson, Brent Johnston, Tong Jun Lin

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

51 Citas (Scopus)

Resumen

Pseudomonas aeruginosa is a major opportunistic pathogen. However, host defense mechanisms involved in P. aeruginosa lung infection remain incompletely defined. The transcription factor IFN regulatory factor 3 (IRF3) is primarily associated with host defense against viral infections, and a role of IRF3 in P. aeruginosa infection has not been reported previously. In this study, we showed that IRF3 deficiency led to impaired clearance of P. aeruginosa from the lungs of infected mice. P. aeruginosa infection induced IRF3 translocation to the nucleus, activation of IFN-stimulated response elements (ISRE), and production of IFN-β, suggesting that P. aeruginosa activates the IRF3-ISRE-IFN pathway. In vitro, macrophages from IRF3-deficient mice showed complete inhibition of CCL5 (RANTES) and CXCL10 (IP-10) production, partial inhibition of TNF, but no effect on CXCL2 (MIP-2) or CXCL1 (keratinocyte-derived chemokine) in response to P. aeruginosa stimulation. In vivo, IRF3-deficient mice showed complete inhibition of CCL5 production and partial or no effects on production of other cytokines and chemokines in the bronchoalveolar lavage fluids and lung tissues. Profiling of immune cells in the airways revealed that neutrophil and macrophage recruitment into the airspace was reduced, whereas B cell, T cell, NK cell, and NKT cell infiltration was unaffected in IRF3-deficient mice following P. aeruginosa lung infection. These data suggest that IRF3 regulates a distinct profile of cytokines and chemokines and selectively modulates neutrophil and macrophage recruitment during P. aeruginosa infection. Thus, IRF3 is an integral component in the host defense against P. aeruginosa lung infection.

Idioma originalEnglish
Páginas (desde-hasta)3602-3609
Número de páginas8
PublicaciónJournal of Immunology
Volumen185
N.º6
DOI
EstadoPublished - sep. 15 2010

ASJC Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

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Citar esto

Carrigan, S. O., Junkins, R., Yang, Y. J., MacNeil, A., Richardson, C., Johnston, B., & Lin, T. J. (2010). IFN regulatory factor 3 contributes to the host response during Pseudomonas aeruginosa lung infection in mice. Journal of Immunology, 185(6), 3602-3609. https://doi.org/10.4049/jimmunol.0903429