A genomic storm in critically injured humans.
A genomic storm in critically injured humans.
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DOI：
10.1084/jem.20111354
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发表时间：
2011-12-19
期刊：
影响因子：
--
通讯作者：
Inflammation and Host Response to Injury Large-Scale Collaborative Research Program
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文献类型：
--
作者：
Xiao W;Mindrinos MN;Seok J;Cuschieri J;Cuenca AG;Gao H;Hayden DL;Hennessy L;Moore EE;Minei JP;Bankey PE;Johnson JL;Sperry J;Nathens AB;Billiar TR;West MA;Brownstein BH;Mason PH;Baker HV;Finnerty CC;Jeschke MG;López MC;Klein MB;Gamelli RL;Gibran NS;Arnoldo B;Xu W;Zhang Y;Calvano SE;McDonald-Smith GP;Schoenfeld DA;Storey JD;Cobb JP;Warren HS;Moldawer LL;Herndon DN;Lowry SF;Maier RV;Davis RW;Tompkins RG;Inflammation and Host Response to Injury Large-Scale Collaborative Research Program
人类的严重损伤诱导基因组风暴，同时改变先天性和适应性免疫基因的表达。人类从损伤中存活需要适当的炎症和免疫反应。我们描述了严重创伤和烧伤后以及接受低剂量细菌内毒素的健康受试者中循环白细胞转录组，并表明这些严重压力会产生全局重新优先顺序，影响>80%的细胞功能和途径，这是一场真正意想不到的“基因组风暴”。在严重的钝性创伤中，早期白细胞基因组反应与全身炎症、先天性免疫和代偿性免疫应答相关基因表达的同时增加以及适应性免疫相关基因的抑制一致。此外，并发症如院内感染和器官衰竭与第二次打击的任何基因组证据无关，不同之处仅在于这种基因组重新优先化的幅度和持续时间。不同损伤之间基因表达模式的相似性揭示了人类对严重炎症应激的明显基本反应，令人惊讶的是，基因组签名远比不同的更常见。基于这些转录数据，我们提出了一个新的范式，人类免疫反应严重损伤。
Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes. Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.
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