Comparative Kinetics of Escherichia coli- and Staphylococcus aureus-Specific Activation of Key Immune Pathways in Mammary Epithelial Cells Demonstrates That S. aureus Elicits a Delayed Response Dominated by Interleukin-6 (IL-6) but Not by IL-1A or Tumor Necrosis Factor Alpha
Comparative Kinetics of Escherichia coli- and Staphylococcus aureus-Specific Activation of Key Immune Pathways in Mammary Epithelial Cells Demonstrates That S. aureus Elicits a Delayed Response Dominated by Interleukin-6 (IL-6) but Not by IL-1A or Tumor Necrosis Factor Alpha
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DOI：
10.1128/iai.01071-10
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发表时间：
2011-02-01
影响因子：
3.1
通讯作者：
Seyfert, Hans-Martin
中科院分区：
文献类型：
--
作者：
Guenther, Juliane;Esch, Kathrin;Seyfert, Hans-Martin
大肠杆菌引起的乳房感染经常引起急性炎症，而金黄色葡萄球菌感染往往引起轻度、亚临床炎症和持续性感染。不同疾病模式的分子原因知之甚少。因此，我们分析了原代牛乳腺上皮细胞（MEC）用热灭活的E. coli或S.金黄色葡萄球菌E.大肠杆菌中迅速而强烈地诱导细胞因子和杀菌因子的表达。S.金黄色葡萄球菌引起反应迟缓，不能快速诱导杀菌因子的表达。两种病原体诱导相似的趋化因子模式，使细胞募集到乳房中，但E。大肠杆菌刺激它们的合成更快更强。大肠杆菌唯一且最强烈上调的基因。大肠杆菌中的肿瘤坏死因子α（TNF-α）和白细胞介素-1（IL-1）可能聚集成一个调控网络。相反，这些主要细胞因子的表达几乎不受S。金黄色。这两种病原体都能迅速引发IL-6的表达增强。在MEC中完全消除MyD 88依赖性Toll样受体（TLR）信号传导后，这仍然是可能的。急诊大肠杆菌特异性强诱导TNF-α和IL-1表达可能是导致动物患大肠杆菌的严重炎症症状的原因。大肠杆菌乳腺炎，而避免快速诱导杀菌因子的合成可能支持S.乳房内的金黄色葡萄球菌。我们建议S.金黄色葡萄球菌破坏了MEC中MyD 88依赖的免疫基因表达激活。
Infections of the udder by Escherichia coli very often elicit acute inflammation, while Staphylococcus aureus infections tend to cause mild, subclinical inflammation and persistent infections. The molecular causes underlying the different disease patterns are poorly understood. We therefore profiled the kinetics and extents of global changes in the transcriptome of primary bovine mammary epithelial cells (MEC) after challenging them with heat-inactivated preparations of E. coli or S. aureus pathogens. E. coli swiftly and strongly induced an expression of cytokines and bactericidal factors. S. aureus elicited a retarded response and failed to quickly induce an expression of bactericidal factors. Both pathogens induced similar patterns of chemokines for cell recruitment into the udder, but E. coli stimulated their synthesis much faster and stronger. The genes that are exclusively and most strongly upregulated by E. coli may be clustered into a regulatory network with tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) in a central position. In contrast, the expression of these master cytokines is barely regulated by S. aureus. Both pathogens quickly trigger an enhanced expression of IL-6. This is still possible after completely abrogating MyD88-dependent Toll-like receptor (TLR) signaling in MEC. The E. coli-specific strong induction of TNF-alpha and IL-1 expression may be causative for the severe inflammatory symptoms of animals suffering from E. coli mastitis, while the avoidance to quickly induce the synthesis of bactericidal factors may support the persistent survival of S. aureus within the udder. We suggest that S. aureus subverts the MyD88-dependent activation of immune gene expression in MEC.