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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-\u03b1) and elevated protein levels of NLRP3, caspase-1, and IL-1\u03b2. Concurrently, SS2 infection reduces miR-7a-5p expression. Dual-luciferase reporter assays confirm that miR-7a-5p directly targets the 3\u2032UTR 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-1\u03b2, 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.<\/jats:p>","DOI":"10.3390\/microorganisms13081924","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T11:31:37Z","timestamp":1755516697000},"page":"1924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["miR-7a-5p Contributes to Suppressing NLRP3\/Caspase-1 Signaling Pathway in Response to Streptococcus suis Type 2 Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Ziteng","family":"Deng","sequence":"first","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Kunyu Integrated Agricultural Research Insititute, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi 848116, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Che","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiedan","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshu","family":"Zhan","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinqin","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7136-5849","authenticated-orcid":false,"given":"Qiang","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China"},{"name":"Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, S., Wang, G., Tang, Y.-D., Li, S., Qin, L., Wang, M., Yang, Y.-B., Gottschalk, M., and Cai, X. 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