miR-223-3p contributes to suppressing NLRP3 inflammasome activation in Streptococcus equi ssp. zooepidemicus infection

Vet Microbiol. 2022 Jun:269:109430. doi: 10.1016/j.vetmic.2022.109430. Epub 2022 Apr 6.

Abstract

Streptococcus equi subsp. zooepidemicus (SEZ) is an essential pathogen in a range of species, causing a worldwide variety of diseases, such as meningitis, endocarditis, and septicaemia. Studies have shown that microRNAs (miRNAs), which regulate target genes at the post-transcriptional level, play an important regulatory role in the organism. In this study, the infection of J774A.1 murine macrophages with SEZ up-regulated NLRP3 inflammasome and downstream pathways accompanied by miR-223-3p down-regulation. Through computational prediction and experimental confirmation, we have shown that miR-223-3p directly targets the NLRP3 mRNA. Consequently, overexpression of miR-223-3p suppressed NLRP3 inflammasome activation and downstream pathways in response to SEZ infection. The miR-223-3p inhibitor exhibited the opposite effect, causing hyperactivation of NLRP3 inflammation activation and downstream pathways. Additionally, we further demonstrated that miRNA-223-3p inhibited the secretion of IL-1β and IL-18 by regulating the NLRP3/caspase-1 pathway. Furthermore, intravenous administration of miR-223-3p significantly decreased inflammation in mice in response to SEZ. In conclusion, our results demonstrated that miR-223-3p contributes to suppressing the NLRP3 inflammasome activation in SEZ infection, contributing novel evidence to identify a therapeutic target for treating SEZ.

Keywords: Inflammation; NLRP3; Streptococcus equi subsp. zooepidemicus; miR-223–3p.

MeSH terms

  • Animals
  • Inflammasomes / genetics
  • Inflammasomes / metabolism
  • Inflammation / metabolism
  • Inflammation / veterinary
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Streptococcal Infections* / veterinary
  • Streptococcus equi* / genetics
  • Streptococcus equi* / metabolism

Substances

  • Inflammasomes
  • MIRN223 microRNA, mouse
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse