A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4.
A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4.
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DOI：
10.1038/ni.3028
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发表时间：
2014-12
影响因子：
30.5
通讯作者：
Chaussabel, Damien
中科院分区：
文献类型：
--
作者：
Alsina, Laia;Israelsson, Elisabeth;Altman, Matthew C.;Dang, Kristen K.;Ghandil, Pegah;Israel, Laura;von Bernuth, Horst;Baldwin, Nicole;Qin, Huanying;Jin, Zongbo;Banchereau, Romain;Anguiano, Esperanza;Ionan, Alexei;Abel, Laurent;Puel, Anne;Picard, Capucine;Pascual, Virginia;Casanova, Jean Laurent;Chaussabel, Damien
人体中激酶 IRAK-4 或接头 MyD88 的功能丧失会中断对病原体感知和炎症引发至关重要的途径。然而，令人惊讶的是，具有功能缺失突变的患者仅对有限范围的病原体敏感。我们采用系统方法来研究患者血液体外暴露于 Toll 样受体和白细胞介素 1 受体激动剂以及整个病原体后的转录组反应。对纯化激动剂的反应在整体上被消除，但在暴露于整个病原体后仍存在可变的残留反应。对后一种反应的进一步剖析发现了受 MyD88 或 IRAK-4 功能丧失影响的一小部分免疫转录程序。这项工作介绍了使用系统方法对先天免疫反应进行整体评估，以及人类原发性免疫缺陷的表征。
Loss of function in the kinase IRAK-4 or the adapter MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. Yet patients with loss of function mutations are surprisingly only susceptible to a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients’ blood to Toll-like receptor and interleukin-1 receptor agonists, and whole pathogens. Responses to purified agonists were globally abolished but variable residual responses were present following exposure to whole pathogens. Further dissection of the latter responses identified a narrow repertoire of immune transcriptional programs affected by loss of MyD88 or IRAK-4 function. This work introduces the use of a systems approach for the global assessment of innate immune responses, and the characterization of human primary immunodeficiencies.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1038/nri3151
发表时间：
2012-02-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
32.4
作者：
Miller, LS;O'Connell, RM;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
5.4
作者：
He, Guoan;Ma, Yao;Chou, Szu-Yi;Li, Huihong;Yang, Chingwen;Chuang, Jen-Zen;Sung, Ching-Hwa;Ding, Aihao
通讯作者：
Ding, Aihao
影响因子：
3.4
作者：
Moreira, Lilian O.;El Kasmi, Karim C.;Murray, Peter J.
通讯作者：
Murray, Peter J.