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

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.