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

Cell Commun Signal. 2023 Feb 6;21(1):31. doi: 10.1186/s12964-023-01038-y.

Abstract

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 (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 in A. cantonensis infection. Further investigation verified that CEBPα promotes pyroptosis by activating miR-101b-3p expression in microglia, and microglial pyroptosis further promoted inflammation.

Conclusions: Our results suggest that a CEBPα/miR-101b-3p/pyroptosis pathway may contribute to A. cantonensis infection-induced inflammation and highlight the pro-inflammatory effect of miR-101b-3p. Video Abstract.

Keywords: Angiostrongylus cantonensis; CEBPα; Meningoencephalitis; Microglial pyroptosis; miR-101b-3p.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Angiostrongylus cantonensis* / metabolism
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha
  • Inflammation
  • Meningoencephalitis*
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Microglia / metabolism
  • Pyroptosis

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • MicroRNAs
  • CEBPA protein, mouse