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

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 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 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 inhibitor. The NETs formation in FlgE-treated neutrophils was not affected by the inhibitor or recombinant IL17A alone but partly impaired in the presence of duanyu18133 pathway inhibition. In conclusion, we propose that the pro-inflammatory activities of FlgE are mediated by activating duanyu18133 phosphorylation and IL17A/IL17R expression and by promoting a NETs formation.

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