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Updated: Jun 10, 2026
Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
IFN regulatory factor 3 contributes to the host response during Pseudomonas aeruginosa lung infection in mice
Svetlana O Carrigan1, Robert Junkins, Yong Jun Yang
1Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Abstract:
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-beta, 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.
Insights
Interferon regulatory factor 3 (IRF3) plays a key role in defending against Pseudomonas aeruginosa lung infections by controlling immune cell recruitment and cytokine production. IRF3 deficiency impairs bacterial clearance, highlighting its importance in host defense.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a significant opportunistic pathogen causing lung infections.
- Host defense mechanisms against P. aeruginosa are not fully understood.
- The role of Interferon regulatory factor 3 (IRF3) in bacterial infections, particularly P. aeruginosa, is previously unreported.
Purpose of the Study:
- To investigate the role of IRF3 in host defense against P. aeruginosa lung infection.
- To elucidate the mechanisms by which IRF3 influences the immune response to P. aeruginosa.
Main Methods:
- Utilized IRF3-deficient mice to assess bacterial clearance and immune responses following P. aeruginosa lung infection.
- Analyzed cytokine and chemokine production in vitro and in vivo.
- Examined immune cell infiltration in the airways using flow cytometry.
Main Results:
- IRF3 deficiency resulted in impaired clearance of P. aeruginosa from the lungs.
- P. aeruginosa infection induced IRF3 nuclear translocation, ISRE activation, and IFN-beta production.
- IRF3 modulated the production of specific cytokines (CCL5, CXCL10, TNF) and chemokines.
- Neutrophil and macrophage recruitment into the airways was reduced in IRF3-deficient mice.
Conclusions:
- IRF3 is crucial for effective host defense against P. aeruginosa lung infection.
- IRF3 regulates a distinct set of cytokines and chemokines.
- IRF3 selectively influences neutrophil and macrophage recruitment during P. aeruginosa infection.
- The IRF3-ISRE-IFN pathway is activated during P. aeruginosa infection.
