IRF3 Inhibits Neutrophil Recruitment in Mice Infected with Pseudomonas aeruginosa
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Pseudomonas aeruginosa is the major cause of morbidity and mortality in patients with ventilator-associated pneumonia. Interferon regulatory factor 3 (IRF3) is a transcription factor that plays an important role in the immune response to viral infection via the IRF3/IFN-β signaling pathway. Controversial data exist regarding the role of IRF3 in immune cell recruitment during bacterial infections. IRF3 has been shown to promote neutrophil recruitment and bacterial clearance in mice infected with P. aeruginosa by inducing the production of specific chemokines and cytokines. In contrast, our study showed that IRF3 knockout (KO) mice infected with P. aeruginosa exhibited greater survival rates, demonstrated enhanced bacterial clearance, and showed significantly increased neutrophil recruitment to the lungs, when compared with the wild-type (WT) mice. The peritoneal lavage fluid collected from IRF3 KO mice 4 h after intraperitoneal injection with P. aeruginosa or 3% thioglycolate contained a significantly increased number of neutrophils. Furthermore, neutrophils from the bone marrow (BM) of IRF3 KO mice showed greater adhesiveness to the extracellular matrix when compared with those of WT mice, post-P. aeruginosa infection. In addition, IRF3 induced the expression of target genes in WT neutrophils infected with P. aeruginosa. These findings indicate that IRF3 exacerbates P. aeruginosa-induced mortality in mice by inhibiting neutrophil adhesion and recruitment to the lungs. Together, these data indicate that the inhibition of IRF3 might provide a possible mechanism for controlling P. aeruginosa infections.
KEY WORDSIRF3 Neutrophil Recruitment Pseudomonas aeruginosa
Bronchoalveolar lavage fluid
Cecal ligation and puncture
- IRF3 KO
Interferon regulatory factor 3
Peritoneal lavage fluid
This work was supported by the Nature Science funding sponsored by Zhejiang Provincial (KZ13058) and Research fund from Hangzhou Normal University (PD12002004121).
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Conflicts of Interest
The authors declare that they have no conflicts of interest.
Zhenghao Piao designed and performed the experiments, analyzed the data, and wrote the manuscript. Haiying Yuan assisted in the writing of this manuscript, and Cuili Wang performed some of the experiments. Liyun Shi helped in the experimental design and edited the manuscript.
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