Clinical and vaccine immunology : CVI · 2014
Systems immunology reveals markers of susceptibility to West Nile virus infection.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Qian Feng, Goel Gautam, Meng Hailong, Wang Xiaomei, You Fuping, Devine Lesley, Raddassi Khadir, Garcia Melissa N, Murray Kristy O, Bolen Christopher R, Gaujoux Renaud, Shen-Orr Shai S, Hafler David, Fikrig Erol, Xavier Ramnik, Kleinstein Steven H, Montgomery Ruth R
Аннотация
West Nile virus (WNV) infection is usually asymptomatic but can cause severe neurological disease and death, particularly in older patients, and how individual variations in immunity contribute to disease severity is not yet defined. Animal studies identified a role for several immunity-related genes that determine the severity of infection. We have integrated systems-level transcriptional and functional data sets from stratified cohorts of subjects with a history of WNV infection to define whether these markers can distinguish susceptibility in a human population. Transcriptional profiles combined with immunophenotyping of primary cells identified a predictive signature of susceptibility that was detectable years after acute infection (67% accuracy), with the most prominent alteration being decreased IL1B induction following ex vivo infection of macrophages with WNV. Deconvolution analysis also determined a significant role for CXCL10 expression in myeloid dendritic cells. This systems analysis identified markers of pathogenic mechanisms and offers insights into potential therapeutic strategies.