CEBPα/miR-101b-3p promotes meningoencephalitis in mice infected with Angiostrongylus cantonensis by promoting microglial pyroptosis

Abstract

AbstractBackgroundAngiostrongylus cantonensis(A. cantonensis) infection can induce acute inflammation, which causes meningoencephalitis and tissue mechanical injury to the brain. Parasite infection–induced microRNAs play important roles in anti-parasite immunity in non-permissive hosts. miR-101b-3p is highly expressed afterA. cantonensisinfection; however, the role of miR-101b-3p and the transcription regulation of miR-101b-3p inA. cantonensisinfection remain poorly characterized.ResultsIn the present study, we found that miR-101b-3p inhibition alleviated inflammation infiltration and pyroptosis inA. cantonensisinfection. In addition, we found that CCAAT/enhancer-binding protein alpha (CEBPα) directly bound to the − 6-k to − 3.5-k region upstream of miR-101b, and CEBPα activated miR-101b-3p expression in microglia. These data suggest the existence of a novel CEBPα/miR-101b-3p/pyroptosis pathway inA. cantonensisinfection. Further investigation verified that CEBPα promotes pyroptosis by activating miR-101b-3p expression in microglia, and microglial pyroptosis further promoted inflammation.ConclusionsOur results suggest that a CEBPα/miR-101b-3p/pyroptosis pathway may contribute toA. cantonensisinfection–induced inflammation and highlight the pro-inflammatory effect of miR-101b-3p.