Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes
Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes
复制标题
母牛分枝杆菌疫苗对小鼠结核病模型的影响：保护作用和差异表达基因
DOI：
10.1186/s40779-020-00258-4
复制
发表时间：
2020-06-03
影响因子：
21.1
通讯作者：
Wu, Xue-Qiong
中科院分区：
文献类型：
--
作者：
Gong, Wen-Ping;Liang, Yan;Wu, Xue-Qiong
背景
结核病是全世界的主要死因。BCG是一种有效的疫苗，但由于各种问题，在世界许多地区没有广泛使用。母牛分枝杆菌（M. Vaccae）是另一种用于人类受试者以预防结核病的疫苗。在本研究中，我们研究了M.通过测定感染M.结核病前后M.牛痘疫苗。
方法
暴露于M.结核杆菌H37 Rv株（5 × 105 CFU）感染成年BALB/c小鼠，随机接种M.通过肌内注射接种牛痘疫苗（22.5 μg）或溶媒（n = 8）。在初次免疫后14天和28天进行加强免疫。通过微阵列和标准生物信息学分析鉴定差异表达的基因。
结果
M.母牛疫苗接种可提供抗M.肺结核感染（最常见于肺部）。我们在接种疫苗的小鼠中鉴定了2326个上调和2221个下调基因。这些变化可以映射到总共123个信号通路（68个上调和55个下调）。进一步的分析指出，MyD 88依赖性TLR信号通路和PI 3 K-Akt信号通路最有可能是功能性的。
结论
M.母牛菌苗对小鼠抗M.结核感染，通过一系列高度复杂的分子变化。本研究结果可为开发更有效的结核病疫苗提供线索。
Background
Tuberculosis is a leading cause of death worldwide. BCG is an effective vaccine, but not widely used in many parts of the world due to a variety of issues. Mycobacterium vaccae (M. vaccae) is another vaccine used in human subjects to prevent tuberculosis. In the current study, we investigated the potential mechanisms of M. vaccae vaccination by determining differentially expressed genes in mice infected with M. tuberculosis before and after M. vaccae vaccination.
Methods
Three days after exposure to M. tuberculosis H37Rv strain (5 × 105 CFU), adult BALB/c mice randomly received either M. vaccae vaccine (22.5 μg) or vehicle via intramuscular injection (n = 8). Booster immunization was conducted 14 and 28 days after the primary immunization. Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis.
Results
M. vaccae vaccination provided protection against M. tuberculosis infection (most prominent in the lungs). We identified 2326 upregulated and 2221 downregulated genes in vaccinated mice. These changes could be mapped to a total of 123 signaling pathways (68 upregulated and 55 downregulated). Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3K-Akt signaling pathway as most likely to be functional.
Conclusions
M. vaccae vaccine provided good protection in mice against M. tuberculosis infection, via a highly complex set of molecular changes. Our findings may provide clue to guide development of more effective vaccine against tuberculosis.