IRF3 Inhibits Neutrophil Recruitment in Mice Infected with Pseudomonas aeruginosa.
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.
Department of Basic Medical Science, School of Medicine, Hangzhou Normal University, Xuelin Street 16#, Hangzhou, 310036, China. parkzhh@hznu.edu.cn.
Zhenghao
Z
Piao
Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Haiying
H
Yuan
Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Cuili
C
Wang
Department of Immunology, Nanjing University of Chinese Medicine, 138 Xianlin Rd, Nanjing, 210023, China. shi_liyun@msn.com.
Liyun
L
Shi
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000473:pathology*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000517:prevention & control; D011550:Pseudomonas aeruginosa
D050838:Interferon Regulatory Factor-3
IRF3; Neutrophil; Pseudomonas aeruginosa; Recruitment