Establishment and transcriptomic analysis of the mouse model of meningitis caused by Streptococcus suis serotype 2

Abstract:

[Background] Streptococcus suis serotype 2 (S. suis 2) causes severe meningitis in the host, posing a major threat to the pig industry and human public health. [Objective] The mouse model of meningitis induced by S. suis 2 infection was established, and its brain tissue was analyzed by transcriptomics to provide a theoretical basis for revealing the molecular mechanism of meningitis caused by S. suis 2 infection in mouse and discovering potential therapeutic targets.[Methods] S. suis 2 was used to infect mouse, and the histopathological changes in the mouse brain tissue were observed to verify the model of meningitis in mouse was successfully established. Furthermore, transcriptomic analysis was performed to identify the differentially expressed genes (DEGs) between the S. suis 2-infected and uninfected mouse. Moreover, gene ontology (GO) functional annotation, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, and Venn analysis were performed for the DEGs. [Results] S. suis 2 successfully infected mouse and caused meningitis. The brain of the infected mouse showed infiltration of massive inflammatory cells and perivascular cuffing around the blood vessels. Moreover, the S. suis 2 strain was isolated from the tissues of the modeled mouse. The results proved that the mouse model of meningitis caused by S. suis 2 infection was successfully established. A total of 397 DEGs were identified, including 109 genes with down-regulated expression and 288 genes with up-regulated expression. GO functional annotation showed that the DEGs were mainly enriched in the cytoplasm, plasma membrane, signal transduction, regulation of transcription, apoptotic process, immune system process, response to bacteria, and protein binding. KEGG pathway enrichment analysis indicated that the DEGs were mainly enriched in multiple important signaling pathways regulating host cytokine-cytokine receptor interaction, immune response, apoptosis, phagocytosis, and metabolism. The Venn analysis showed that the brain-derived neurotrophic factor (bdnf) gene converged in meningitis-related genes set, deafness-related genes set, and DEGs set of S. suis 2 infection, with significantly down-regulated expression. The c4b, fas, icam1, cxcl1, csf3, lrg1, and nde1 genes converged in the meningitis-related genes set and the DEGs set of S. suis 2 infection, with significantly up-regulated expression. [Conclusion] A mouse model of meningitis induced by S. suis 2 infection was successfully established. The transcriptomics of the brain tissue of the model mouse revealed several key DEGs and signaling pathways, and the molecular signaling pathway network was built. The findings provide a new theoretical basis for revealing the molecular mechanism of S. suis 2 induced-meningitis and exploring potential therapeutic targets.

Key words:Streptococcus suis serotype 2;infection;meningitis;transcriptomics;immune response