Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family
Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family
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DOI：
10.1038/emboj.2011.94
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发表时间：
2011-05-18
期刊：
影响因子：
11.4
通讯作者：
Vogel, Joerg
中科院分区：
文献类型：
--
作者：
Schulte, Leon N.;Eulalio, Ana;Vogel, Joerg
MicroRNA在真核宿主对病毒和细胞外细菌病原体的应答中具有公认的作用。相比之下，microRNA对入侵细菌的反应仍然未知。在这里，我们报告细胞类型依赖性microRNA的监管哺乳动物细胞感染肠侵袭性病原体，鼠伤寒沙门氏菌。小鼠巨噬细胞强烈上调NF-κ B相关microRNA;引人注目的是，无论宿主是否成功入侵和/或复制，或者是否发生炎症反应，这些由细菌脂多糖（LPS）诱导的调节都会发生并持续存在，这表明microRNA属于抗细菌防御的第一道防线。然而，内毒素耐受性巨噬细胞中全局免疫调节剂miR-155的抑制揭示了microRNA反应也取决于感染细胞的状态。这项研究确定了let-7家族作为巨噬细胞和上皮细胞中沙门氏菌调节的microRNA的共同特征，并表明let-7的抑制减轻了负转录后控制的细胞因子IL-6和IL-10 mRNA。我们的研究结果建立了一个范例microRNA介导的前馈激活的炎症因子时，哺乳动物细胞的细菌病原体的目标。EMBO Journal（2011）30，1977-1989。doi：10.1038/daj.2011.94; 2011年4月5日在线发布
MicroRNAs have well-established roles in eukaryotic host responses to viruses and extracellular bacterial pathogens. In contrast, microRNA responses to invasive bacteria have remained unknown. Here, we report cell type-dependent microRNA regulations upon infection of mammalian cells with the enteroinvasive pathogen, Salmonella Typhimurium. Murine macrophages strongly upregulate NF-kappa B associated microRNAs; strikingly, these regulations which are induced by bacterial lipopolysaccharide (LPS) occur and persist regardless of successful host invasion and/or replication, or whether an inflammatory response is mounted, suggesting that microRNAs belong to the first line of anti-bacterial defence. However, a suppression of the global immune regulator miR-155 in endotoxin-tolerant macrophages revealed that microRNA responses also depend on the status of infected cells. This study identifies the let-7 family as the common denominator of Salmonella-regulated microRNAs in macrophages and epithelial cells, and suggests that repression of let-7 relieves cytokine IL-6 and IL-10 mRNAs from negative post-transcriptional control. Our results establish a paradigm of microRNA-mediated feed-forward activation of inflammatory factors when mammalian cells are targeted by bacterial pathogens. The EMBO Journal (2011) 30, 1977-1989. doi: 10.1038/emboj.2011.94; Published online 5 April 2011