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Inflammation

, Volume 40, Issue 3, pp 735–744 | Cite as

IRF3 Inhibits Neutrophil Recruitment in Mice Infected with Pseudomonas aeruginosa

  • Zhenghao PiaoEmail author
  • Haiying Yuan
  • Cuili Wang
  • Liyun ShiEmail author
ORIGINAL ARTICLE

Abstract

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 WORDS

IRF3 Neutrophil Recruitment Pseudomonas aeruginosa 

Abbreviations

BALF

Bronchoalveolar lavage fluid

BM

Bone marrow

CLP

Cecal ligation and puncture

IRF3 KO

IRF3 knockout

IRF3

Interferon regulatory factor 3

PLF

Peritoneal lavage fluid

WT

Wild type

Notes

Acknowledgments

This work was supported by the Nature Science funding sponsored by Zhejiang Provincial (KZ13058) and Research fund from Hangzhou Normal University (PD12002004121).

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authorship

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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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Basic Medical Science, School of MedicineHangzhou Normal UniversityHangzhouChina
  2. 2.Department of Clinical Laboratory, Women’s Hospital, School of MedicineZhejiang UniversityHangzhouChina
  3. 3.Kidney Disease Center, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouChina
  4. 4.Department of ImmunologyNanjing University of Chinese MedicineNanjingChina

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