Kobzik Lester
Department of Environmental Health, Harvard T.H. Chan School of Public Health, and Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
J Innate Immun. 2017;9(3):232-242. doi: 10.1159/000457902. Epub 2017 Mar 1.
Excess or dysregulated host inflammatory responses cause much of the morbidity and mortality caused by severe influenza. Given the limitations of vaccines and antiviral drugs, novel therapeutics to modulate host responses and improve outcomes in severe influenza are needed. One strategy is to learn from the direct comparison of high-survivor versus high-mortality animal models. This review surveys the results of lung transcriptome profiling studies in murine models that directly compare susceptible versus resistant hosts challenged with identical influenza infections. The potential contributions and limitations of these studies are discussed. To amplify their power, the studies are subjected to a meta-analysis, which helps identify frequently dysregulated pathways and potentially novel areas for investigation. Using connectivity map-based tools (LINCS), transcriptome signatures linked to susceptibility can identify candidate drugs that merit testing for in vivo efficacy.
宿主炎症反应过度或失调是导致严重流感相关发病率和死亡率的主要原因。鉴于疫苗和抗病毒药物的局限性，需要新型疗法来调节宿主反应并改善严重流感的预后。一种策略是通过直接比较高存活率与高死亡率的动物模型来获取经验。本综述调查了小鼠模型中肺转录组谱分析研究的结果，这些研究直接比较了受到相同流感感染的易感宿主与抗性宿主。讨论了这些研究的潜在贡献和局限性。为了增强其效力，对这些研究进行了荟萃分析，这有助于识别经常失调的途径和潜在的新研究领域。使用基于连通性图谱的工具（LINCS），与易感性相关的转录组特征可以识别值得测试其体内疗效的候选药物。
