Priming of Natural Killer Cells by Nonmucosal Mononuclear Phagocytes Requires Instructive Signals from Commensal Microbiota
Priming of Natural Killer Cells by Nonmucosal Mononuclear Phagocytes Requires Instructive Signals from Commensal Microbiota
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DOI：
10.1016/j.immuni.2012.05.020
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发表时间：
2012-07-27
期刊：
影响因子：
32.4
通讯作者：
Diefenbach, Andreas
中科院分区：
文献类型：
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作者：
Ganal, Stephanie C.;Sanos, Stephanie L.;Diefenbach, Andreas
单核吞噬细胞是先天免疫系统的一个重要组成部分，该系统被视为在遇到病原体时能立即作出反应的系统。在此，我们表明，在微生物刺激下，无菌小鼠非黏膜淋巴器官中的单核吞噬细胞无法诱导一组炎症反应基因的表达，包括那些编码各种I型干扰素（IFN - I）的基因。因此，自然杀伤（NK）细胞的激活以及抗病毒免疫受到严重损害。虽然无菌小鼠的单核吞噬细胞中模式识别受体信号传导以及转录因子NF - κB和IRF3的核转位是正常的，但它们与各自细胞因子启动子的结合受损，这与激活组蛋白标记的缺失相关。我们的数据揭示了出生后定殖的微生物群在单核吞噬细胞系统中引入染色质水平变化方面此前未被认识到的作用，从而使关键炎症基因的表达处于准备状态，以便在病毒感染期间启动强大的全身性免疫反应。
Mononuclear phagocytes are an important component of an innate immune system perceived as a system ready to react upon encounter of pathogens. Here, we show that in response to microbial stimulation, mononuclear phagocytes residing in nonmucosal lymphoid organs of germ-free mice failed to induce expression of a set of inflammatory response genes, including those encoding the various type I interferons (IFN-I). Consequently, NK cell priming and antiviral immunity were severely compromised. Whereas pattern recognition receptor signaling and nuclear translocation of the transcription factors NF-kappa B and IRF3 were normal in mononuclear phagocytes of germ-free mice, binding to their respective cytokine promoters was impaired, which correlated with the absence of activating histone marks. Our data reveal a previously unrecognized role for postnatally colonizing microbiota in the introduction of chromatin level changes in the mononuclear phagocyte system, thereby poising expression of central inflammatory genes to initiate a powerful systemic immune response during viral infection.