miR-7a-5p Contributes to Suppressing NLRP3/Caspase-1 Signaling Pathway in Response to Streptococcus suis Type 2
Ziteng Deng1,2, Qian Sun1,2, Shun Li1,3
1School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China.
Abstract:
Streptococcus suis type 2 (SS2) is a pathogen causing diseases like meningitis and septicaemia worldwide. While microRNAs (miRNAs) are acknowledged for their role in post-transcriptional regulation of gene expression and influence on immune responses, their exact functions in hosts during SS2 infection remain elusive. This study aims to explore the role of miR-7a-5p in macrophages during SS2 infection. Our findings reveal that SS2 infection in J774A.1 cells triggers upregulation of the NLRP3 inflammasome signaling pathways, evidenced by enhanced mRNA expression of pro-inflammatory cytokines (IL-6, IL-18, IL-23, TNF-α) and elevated protein levels of NLRP3, caspase-1, and IL-1β. Concurrently, SS2 infection reduces miR-7a-5p expression. Dual-luciferase reporter assays confirm that miR-7a-5p directly targets the 3'UTR of NLRP3 mRNA. Notably, miR-7a-5p overexpression in SS2-infected J774A.1 cells suppresses NLRP3 inflammasome activation and downstream signaling, as demonstrated by reduced mRNA levels of inflammatory mediators and decreased protein levels of NLRP3, caspase-1, IL-1β, and IL-18. Conversely, miR-7a-5p inhibition produces effects opposite to those of overexpression. In mice, administration of miR-7a-5p mimics mitigates SS2-induced lung, liver, and spleen damage, reducing histological scores in these organs. Collectively, these results show that miR-7a-5p alleviates SS2-induced inflammation by inhibiting the NLRP3 inflammasome, underscoring its potential as a therapeutic target for SS2-associated diseases.
Insights
MicroRNA-7a-5p (miR-7a-5p) inhibits the NLRP3 inflammasome, reducing inflammation caused by Streptococcus suis type 2 (SS2) infection. This finding highlights miR-7a-5p as a potential therapeutic target for SS2-related diseases.
Area of Science:
- Immunology
- Molecular Biology
- Microbiology
Background:
- Streptococcus suis type 2 (SS2) causes severe diseases like meningitis and septicaemia globally.
- MicroRNAs (miRNAs) regulate gene expression and immune responses, but their role in SS2 infection is unclear.
- The NLRP3 inflammasome is a key mediator of inflammation in response to various pathogens.
Purpose of the Study:
- To investigate the role of miR-7a-5p in macrophages during SS2 infection.
- To determine if miR-7a-5p targets and regulates the NLRP3 inflammasome pathway.
- To evaluate the therapeutic potential of miR-7a-5p in mitigating SS2-induced pathology.
Main Methods:
- Infection of J774A.1 macrophage cells with SS2.
- Measurement of pro-inflammatory cytokine mRNA and protein levels.
- Dual-luciferase reporter assays to confirm miR-7a-5p targeting of NLRP3.
- In vivo studies using a mouse model of SS2 infection treated with miR-7a-5p mimics.
Main Results:
- SS2 infection upregulated NLRP3 inflammasome components and pro-inflammatory cytokines while downregulating miR-7a-5p.
- miR-7a-5p directly targets the 3'UTR of NLRP3 mRNA.
- Overexpression of miR-7a-5p suppressed SS2-induced NLRP3 inflammasome activation and inflammation in vitro and in vivo, reducing organ damage.
Conclusions:
- miR-7a-5p acts as a negative regulator of the NLRP3 inflammasome in response to SS2 infection.
- Restoring miR-7a-5p levels can alleviate SS2-induced inflammation and organ damage.
- miR-7a-5p represents a promising therapeutic candidate for treating SS2-associated diseases.
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