Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom.
South African Tuberculosis Vaccine Initiative and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Institute of Infectious Diseases and Molecular Medicine, Rondebosch, 7701, Cape Town, South Africa.
Sci Rep. 2018 Aug 30;8(1):13086. doi: 10.1038/s41598-018-31537-9.
Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB) and induces highly variable protection against pulmonary disease in different countries. We hypothesised that DNA methylation is one of the molecular mechanisms driving variability in BCG-induced immune responses. DNA methylation in peripheral blood mononuclear cells (PBMC) from BCG vaccinated infants was measured and comparisons made between low and high BCG-specific cytokine responders. We found 318 genes and 67 pathways with distinct patterns of DNA methylation, including immune pathways, e.g. for T cell activation, that are known to directly affect immune responses. We also highlight signalling pathways that could indirectly affect the BCG-induced immune response: potassium and calcium channel, muscarinic acetylcholine receptor, G Protein coupled receptor (GPCR), glutamate signalling and WNT pathways. This study suggests that in addition to immune pathways, cellular processes drive vaccine-induced immune responses. Our results highlight mechanisms that require consideration when designing new TB vaccines.
卡介苗（BCG）是唯一获准用于结核病（TB）的疫苗，在不同国家对肺部疾病的保护作用差异很大。我们假设 DNA 甲基化是驱动卡介苗诱导的免疫反应变异性的分子机制之一。测量了接种卡介苗的婴儿外周血单核细胞（PBMC）中的 DNA 甲基化，并比较了低和高卡介苗特异性细胞因子反应者之间的差异。我们发现了 318 个基因和 67 条具有不同 DNA 甲基化模式的途径，包括已知直接影响免疫反应的 T 细胞激活等免疫途径。我们还强调了可能间接影响卡介苗诱导免疫反应的信号通路：钾和钙通道、毒蕈碱乙酰胆碱受体、G 蛋白偶联受体（GPCR）、谷氨酸信号和 WNT 通路。这项研究表明，除了免疫途径外，细胞过程也会驱动疫苗诱导的免疫反应。我们的研究结果强调了在设计新的结核病疫苗时需要考虑的机制。
