Authors: Zhenghao Piao Haiying Yuan Cuili Wang Liyun Shi
Publish Date: 2017/02/08
Volume: 40, Issue: 3, Pages: 735-744
Abstract
Pseudomonas aeruginosa is the major cause of morbidity and mortality in patients with ventilatorassociated 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/IFNβ 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 wildtype 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 postP 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 aeruginosainduced 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 infectionsZhenghao 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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