Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China.
PLoS One. 2012;7(2):e32150. doi: 10.1371/journal.pone.0032150. Epub 2012 Feb 27.
Streptococcus suis type 2 (SS2) is an important swine pathogen and zoonosis agent. A/J mice are significantly more susceptible than C57BL/6 (B6) mice to SS2 infection, but the genetic basis is largely unknown. Here, alterations in gene expression in SS2 (strain HA9801)-infected mice were identified using Illumina mouse BeadChips. Microarray analysis revealed 3,692 genes differentially expressed in peritoneal macrophages between A/J and B6 mice due to SS2 infection. Between SS2-infected A/J and control A/J mice, 2646 genes were differentially expressed (1469 upregulated; 1177 downregulated). Between SS2-infected B6 and control B6 mice, 1449 genes were differentially expressed (778 upregulated; 671 downregulated). These genes were analyzed for significant Gene Ontology (GO) categories and signaling pathways using the Kyoto Encylopedia of Genes and Genomes (KEGG) database to generate a signaling network. Upregulated genes in A/J and B6 mice were related to response to bacteria, immune response, positive regulation of B cell receptor signaling pathway, type I interferon biosynthesis, defense and inflammatory responses. Additionally, upregulated genes in SS2-infected B6 mice were involved in antigen processing and presentation of exogenous peptides, peptide antigen stabilization, lymphocyte differentiation regulation, positive regulation of monocyte differentiation, antigen receptor-mediated signaling pathway and positive regulation of phagocytosis. Downregulated genes in SS2-infected B6 mice played roles in glycolysis, carbohydrate metabolic process, amino acid metabolism, behavior and muscle regulation. Microarray results were verified by quantitative real-time PCR (qRT-PCR) of 14 representative deregulated genes. Four genes differentially expressed between SS2-infected A/J and B6 mice, toll-like receptor 2 (Tlr2), tumor necrosis factor (Tnf), matrix metalloproteinase 9 (Mmp9) and pentraxin 3 (Ptx3), were previously implicated in the response to S. suis infection. This study identified candidate genes that may influence susceptibility or resistance to SS2 infection in A/J and B6 mice, providing further validation of these models and contributing to understanding of S. suis pathogenic mechanisms.
猪链球菌 2 型（SS2）是一种重要的猪病原体和人畜共患病原。与 C57BL/6（B6）小鼠相比，A/J 小鼠对 SS2 感染的敏感性显著更高，但遗传基础在很大程度上尚不清楚。在这里，我们使用 Illumina 小鼠 BeadChips 鉴定了 SS2（菌株 HA9801）感染小鼠的基因表达变化。微阵列分析显示，由于 SS2 感染，A/J 和 B6 小鼠腹膜巨噬细胞中有 3692 个基因表达差异。与对照 A/J 小鼠相比，在 SS2 感染的 A/J 小鼠中，有 2646 个基因表达差异（1469 个上调；1177 个下调）。与对照 B6 小鼠相比，在 SS2 感染的 B6 小鼠中，有 1449 个基因表达差异（778 个上调；671 个下调）。我们使用京都基因与基因组百科全书（KEGG）数据库对这些基因进行了显著的基因本体论（GO）类别和信号通路分析，以生成信号网络。A/J 和 B6 小鼠中上调的基因与细菌反应、免疫反应、B 细胞受体信号通路的正调控、I 型干扰素生物合成、防御和炎症反应有关。此外，在 SS2 感染的 B6 小鼠中上调的基因参与了外源性肽的抗原加工和呈递、肽抗原稳定、淋巴细胞分化调节、单核细胞分化的正调控、抗原受体介导的信号通路和吞噬作用的正调控。在 SS2 感染的 B6 小鼠中下调的基因参与了糖酵解、碳水化合物代谢过程、氨基酸代谢、行为和肌肉调节。通过 14 个代表性失调基因的定量实时 PCR（qRT-PCR）验证了微阵列结果。在 SS2 感染的 A/J 和 B6 小鼠之间差异表达的 4 个基因，即 Toll 样受体 2（Tlr2）、肿瘤坏死因子（Tnf）、基质金属蛋白酶 9（Mmp9）和 pentraxin 3（Ptx3），之前与猪链球菌感染的反应有关。本研究鉴定了可能影响 A/J 和 B6 小鼠对 SS2 感染易感性或抗性的候选基因，进一步验证了这些模型，并有助于了解猪链球菌的致病机制。
