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

摘要

Background Angiostrongylus 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 after A. cantonensis infection; however, the role of miR-101b-3p and the transcription regulation of miR-101b-3p in A. cantonensis infection remain poorly characterized.Results In the present study, we found that miR-101b-3p inhibition alleviated inflammation infiltration and pyroptosis in A. cantonensis infection. In addition, we found that CCAAT/enhancer-binding protein alpha (CEBP alpha) directly bound to the - 6-k to - 3.5-k region upstream of miR-101b, and CEBP alpha activated miR-101b-3p expression in microglia. These data suggest the existence of a novel CEBP alpha/miR-101b-3p/pyroptosis pathway in A. cantonensis infection. Further investigation verified that CEBP alpha promotes pyroptosis by activating miR-101b-3p expression in microglia, and microglial pyroptosis further promoted inflammation.Conclusions Our results suggest that a CEBP alpha/miR-101b-3p/pyroptosis pathway may contribute to A. cantonensis infection-induced inflammation and highlight the pro-inflammatory effect of miR-101b-3p.

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