Loré Nicola Ivan, Cigana Cristina, Sipione Barbara, Bragonzi Alessandra
Division of Immunology, Transplantation and Infectious Diseases, Infections and Cystic Fibrosis Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Mamm Genome. 2018 Aug;29(7-8):550-557. doi: 10.1007/s00335-018-9753-8. Epub 2018 Jun 12.
Understanding the significance of human genetic diversity in modulating host susceptibility to opportunistic infections is an emerging challenge in the field of respiratory illnesses. While it is recognized that diverse bacterial strains account for differential disease manifestations, emerging data indicate that host genetic diversity is an important determinant factor that influences the severity of opportunistic infections. With particular regard to respiratory illnesses mediated by the gram-negative bacterium Pseudomonas aeruginosa, diverse genetic background is also emerging as a key contributor. Human-genome-wide association studies are a common approach for determining the inter-individual genetic variation associated with variability of the pulmonary infections. Historically, diverse murine inbred mouse strains and ex-vivo cellular models were considered complementary to human studies for establishing the contribution of genetic background to P. aeruginosa respiratory infections. More recently, the development of a new mouse model of infection, mirroring human airway diseases, combined with innovative murine resource populations, modelling human genetic variation, provides additional insights into the mechanisms of genetic susceptibility. In this review, we cover the recent state of the art of human and animal studies and we discuss future potential challenges in the field of P. aeruginosa respiratory infections.
了解人类遗传多样性在调节宿主对机会性感染易感性方面的意义是呼吸系统疾病领域中一个新出现的挑战。虽然人们认识到不同的细菌菌株会导致不同的疾病表现,但新出现的数据表明,宿主遗传多样性是影响机会性感染严重程度的一个重要决定因素。特别是对于由革兰氏阴性菌铜绿假单胞菌介导的呼吸系统疾病,不同的遗传背景也正成为一个关键因素。全人类基因组关联研究是确定与肺部感染变异性相关的个体间遗传变异的常用方法。从历史上看,不同的近交系小鼠品系和体外细胞模型被认为是对人类研究的补充,用于确定遗传背景对铜绿假单胞菌呼吸道感染的影响。最近,一种模拟人类气道疾病的新型感染小鼠模型的开发,结合创新的小鼠资源群体,模拟人类遗传变异,为遗传易感性机制提供了更多见解。在这篇综述中,我们涵盖了人类和动物研究的最新进展,并讨论了铜绿假单胞菌呼吸道感染领域未来可能面临的挑战。