Deng Ziteng, Sun Qian, Li Shun, Wang Yibo, Che Yuxin, Huang Yunfei, Liao Jiedan, Xie Honglin, Zhan Xiaoshu, Sun Qinqin, Fu Qiang
School of Animal Science and Technology, Foshan University, No. 33 Guangyun Road, Foshan 528225, China.
Foshan University Veterinary Teaching Hospital, Foshan University, Foshan 528225, China.
Microorganisms. 2025 Aug 18;13(8):1924. doi: 10.3390/microorganisms13081924.
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.
2型猪链球菌（SS2）是一种在全球范围内可引发脑膜炎和败血症等疾病的病原体。虽然微小RNA（miRNA）因其在基因表达的转录后调控以及对免疫反应的影响而受到认可，但其在SS2感染期间在宿主体内的确切功能仍不清楚。本研究旨在探讨miR-7a-5p在SS2感染期间巨噬细胞中的作用。我们的研究结果表明，J774A.1细胞中的SS2感染会触发NLRP3炎性小体信号通路的上调，促炎细胞因子（IL-6、IL-18、IL-23、TNF-α）的mRNA表达增强以及NLRP3、半胱天冬酶-1和IL-1β的蛋白质水平升高证明了这一点。同时，SS2感染会降低miR-7a-5p的表达。双荧光素酶报告基因检测证实miR-7a-5p直接靶向NLRP3 mRNA的3'UTR。值得注意的是，在受SS2感染的J774A.1细胞中过表达miR-7a-5p可抑制NLRP3炎性小体的激活和下游信号传导，炎性介质的mRNA水平降低以及NLRP3、半胱天冬酶-1、IL-1β和IL-18的蛋白质水平降低证明了这一点。相反，抑制miR-7a-5p会产生与过表达相反的效果。在小鼠中，给予miR-7a-5p模拟物可减轻SS2诱导的肺、肝和脾损伤，降低这些器官的组织学评分。总体而言，这些结果表明miR-7a-5p通过抑制NLRP3炎性小体减轻SS2诱导的炎症，突出了其作为SS2相关疾病治疗靶点的潜力。
