Verhein Kirsten C, Vellers Heather L, Kleeberger Steven R
Inflammation, Immunity, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Inflammation, Immunity, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Dr., Building 101, Rm. D240, Research Triangle Park, NC, 27709, USA.
Mamm Genome. 2018 Feb;29(1-2):38-47. doi: 10.1007/s00335-018-9733-z.
Respiratory infectious diseases resulting from bacterial or viral pathogens such as Mycobacterium tuberculosis, Streptococcus pneumoniae, respiratory syncytial virus (RSV), or influenza, are major global public health concerns. Lower respiratory tract infections are leading causes of morbidity and mortality, only behind ischemic heart disease and stroke (GBD 2015 LRI Collaborators in Lancet Infect Dis 17(11):1133-1161, 2017). Developing countries are particularly impacted by these diseases. However, while many are infected with viruses such as RSV (> 90% of all individuals are infected by age 2), only sub-populations develop severe disease. Many factors may contribute to the inter-individual variation in response to respiratory infections, including gender, age, socioeconomic status, nutrition, and genetic background. Association studies with functional single nucleotide polymorphisms in biologically plausible gene candidates have been performed in human populations to provide insight to the molecular genetic contribution to pulmonary infections and disease severity. In vitro cell models and genome-wide association studies in animal models of genetic susceptibility to respiratory infections have also identified novel candidate susceptibility genes, some of which have also been found to contribute to disease susceptibility in human populations. Genetic background may also contribute to differential efficacy of vaccines against respiratory infections. Development of new genetic mouse models such as the collaborative cross and diversity outbred mice should provide additional insight to the mechanisms of genetic susceptibility to respiratory infections. Continued investigation of susceptibility factors should provide insight to novel strategies to prevent and treat disease that contributes to global morbidity and mortality attributed to respiratory infections.
由细菌或病毒病原体引起的呼吸道传染病，如结核分枝杆菌、肺炎链球菌、呼吸道合胞病毒（RSV）或流感病毒，是全球主要的公共卫生问题。下呼吸道感染是发病和死亡的主要原因，仅次于缺血性心脏病和中风（《柳叶刀·传染病》2017年第17卷第11期，第1133 - 1161页，全球疾病负担研究2015下呼吸道感染协作组）。发展中国家尤其受到这些疾病的影响。然而，虽然许多人感染了RSV等病毒（超过90%的个体在2岁前受到感染），但只有部分人群会发展为严重疾病。许多因素可能导致个体对呼吸道感染反应的差异，包括性别、年龄、社会经济地位、营养和遗传背景。在人群中开展了与生物学上合理的候选基因中功能性单核苷酸多态性的关联研究，以深入了解肺部感染和疾病严重程度的分子遗传贡献。体外细胞模型以及呼吸道感染遗传易感性动物模型的全基因组关联研究也确定了新的候选易感基因，其中一些基因也被发现与人群中的疾病易感性有关。遗传背景也可能导致针对呼吸道感染的疫苗疗效存在差异。新型遗传小鼠模型的开发，如协作杂交小鼠和多样性远交小鼠，应该能为呼吸道感染遗传易感性机制提供更多见解。对易感因素的持续研究应该能为预防和治疗导致全球因呼吸道感染而发病和死亡的疾病的新策略提供见解。
