Neutrophils and IL17A mediate flagellar hook protein FlgE-induced mouse acute lung inflammation

Yuanyuan Li, Ying Shen, Dandan Lin, Hongbo Zhang, Ting Wang, Haiyan Liu, Yiqiang Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Bacterial flagellar hook and recombinant flagellar hook protein E (FlgE) were reportedly immunostimulatory in mammalian cells or tissues. Current study focused on the mechanisms underlying FlgE stimulation. In an acute lung injury model induced by intranasal FlgE challenge, neutrophils were the predominant infiltrates in lungs, and depletion of neutrophils with anti-Ly6G antibody attenuated FlgE-induced lung damage. However, the FlgE-induced neutrophils recruitment, neutrophils reactive oxygen species (ROS) generation, and neutrophil extracellular traps (NETs) formation were significantly impaired in Il17a −/− mice compared with those in wild-type (WT) mice. In FlgE-treated lung organoids and isolated neutrophils, the phosphorylation levels of signal transfer and activator of transcription protein 3 (STAT3), which was involved in neutrophils functions, were upregulated, but this upregulation was partly impaired upon IL17A deficiency or by IL6 neutralisation. When neutrophils isolated from WT mice were treated with FlgE, the expression of IL17A/IL17RC was increased, but the activation was blocked by STAT3 inhibitor. The NETs formation in FlgE-treated neutrophils was not affected by the ROS inhibitor or recombinant IL17A alone but partly impaired in the presence of STAT3 pathway inhibition. In conclusion, we propose that the pro-inflammatory activities of FlgE are mediated by activating STAT3 phosphorylation and IL17A/IL17R expression and by promoting a ROS-independent NETs formation.

Original languageEnglish
Article numbere12975
JournalCellular Microbiology
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 2019
Externally publishedYes

Keywords

  • STAT3
  • acute lung injury
  • flagellar hook protein FlgE
  • interleukin 17A
  • neutrophil extracellular traps

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