MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model.
MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model.
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DOI：
10.1534/g3.113.009936
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发表时间：
2014-01-27
期刊：
影响因子：
--
通讯作者：
Lynn DJ
中科院分区：
文献类型：
--
作者：
Lawless N;Reinhardt TA;Bryan K;Baker M;Pesch B;Zimmerman D;Zuelke K;Sonstegard T;O'Farrelly C;Lippolis JD;Lynn DJ
牛乳腺炎是一种由炎症引起的牛乳腺疾病，每年给全球乳制品行业造成数十亿美元的损失。由于疾病易感性是一个多因素的复杂表型，需要一个综合的生物学方法来剖析所涉及的分子网络。在这里，我们报告了这样一种方法，使用下一代测序结合先进的网络和途径生物学方法，同时在多个时间点（0，12，24，36和48小时）在牛奶和血液中的流式细胞仪分离的CD14+单核细胞在体内感染链球菌的动物mRNA和miRNA的表达谱。超过3700差异表达（DE）基因被确定在牛奶中分离的单核细胞（MIMs），一个关键的免疫细胞招募到感染的网站在乳腺炎。上调基因显著富集炎症途径，而下调基因富集非糖酵解代谢途径。然而，血液中单核细胞转录的变化更为微妙，但突出了这种感染的全身影响。在血液分离的单核细胞（BIM）中上调的基因显示出与干扰素和趋化因子信号传导的显著关联。此外，26个miRNAs在MIM中是DE，3个在BIM中是DE。通路分析显示，下调的miRNA的预测靶点高度富集在先天免疫中的作用（FDR < 3.4E−8），特别是TLR信号传导，而上调的miRNA优先靶向参与代谢的基因。我们的结论是，在S。单核细胞感染miRNAs是单核细胞炎症反应网络的关键放大器和几种代谢途径的阻遏物。
Bovine mastitis is an inflammation-driven disease of the bovine mammary gland that costs the global dairy industry several billion dollars per year. Because disease susceptibility is a multifactorial complex phenotype, an integrative biology approach is required to dissect the molecular networks involved. Here, we report such an approach using next-generation sequencing combined with advanced network and pathway biology methods to simultaneously profile mRNA and miRNA expression at multiple time points (0, 12, 24, 36 and 48 hr) in milk and blood FACS-isolated CD14+ monocytes from animals infected in vivo with Streptococcus uberis. More than 3700 differentially expressed (DE) genes were identified in milk-isolated monocytes (MIMs), a key immune cell recruited to the site of infection during mastitis. Upregulated genes were significantly enriched for inflammatory pathways, whereas downregulated genes were enriched for nonglycolytic metabolic pathways. Monocyte transcriptional changes in the blood, however, were more subtle but highlighted the impact of this infection systemically. Genes upregulated in blood-isolated monocytes (BIMs) showed a significant association with interferon and chemokine signaling. Furthermore, 26 miRNAs were DE in MIMs and three were DE in BIMs. Pathway analysis revealed that predicted targets of downregulated miRNAs were highly enriched for roles in innate immunity (FDR < 3.4E−8), particularly TLR signaling, whereas upregulated miRNAs preferentially targeted genes involved in metabolism. We conclude that during S. uberis infection miRNAs are key amplifiers of monocyte inflammatory response networks and repressors of several metabolic pathways.
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影响因子：
6.7
作者：
Arnaud N;Dabo S;Akazawa D;Fukasawa M;Shinkai-Ouchi F;Hugon J;Wakita T;Meurs EF
通讯作者：
Meurs EF
影响因子：
3.7
作者：
Chen H;Untiveros GM;McKee LA;Perez J;Li J;Antin PB;Konhilas JP
通讯作者：
Konhilas JP
影响因子：
11.4
作者：
Abdullah, Zeinab;Schlee, Martin;Knolle, Percy A.
通讯作者：
Knolle, Percy A.
影响因子：
4.6
作者：
Coutinho, Luiz L.;Matukumalli, Lakshmi K.;Smith, Timothy P. L.
通讯作者：
Smith, Timothy P. L.
影响因子：
4.6
作者：
Guerra, C.;Johal, K.;Venketaraman, V.
通讯作者：
Venketaraman, V.