Genetic susceptibility to S. aureus mastitis in sheep: differential expression of mammary epithelial cells in response to live bacteria or supernatant
Genetic susceptibility to S. aureus mastitis in sheep: differential expression of mammary epithelial cells in response to live bacteria or supernatant
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DOI：
10.1152/physiolgenomics.00155.2011
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发表时间：
2012-04-01
影响因子：
4.6
通讯作者：
Foucras, Gilles
中科院分区：
文献类型：
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作者：
Bonnefont, Cecile M. D.;Rainard, Pascal;Foucras, Gilles
金黄色葡萄球菌是乳反刍动物乳腺炎的常见病原体，是临床和亚临床乳腺炎的原因。乳腺上皮细胞（MEC）不仅是抵抗细菌入侵的物理屏障，而且是先天免疫反应的活跃参与者，允许感染清除。为了破译它们的一般功能，特别是在对葡萄球菌表现出不同水平遗传易感性的动物中，我们用金黄色葡萄球菌刺激了母羊的MEC，这些母羊在乳体细胞数量上有不同的选择。根据活菌或培养上清的刺激条件，研究了MEC反应。在5小时的时间过程中，通过微阵列研究早期MEC反应，以鉴定与宿主遗传背景和刺激条件有关的差异表达基因。在这两种刺激条件下，代谢过程被改变，凋亡相关途径被显著改变，炎症和免疫反应随着il1a、il1b和tnfa以及几种已知可增强中性粒细胞（cxcl8）或单核白细胞（ccl20）募集的趋化因子的上调而增强。氧化应激相关基因在活菌刺激后增加，而免疫反应相关基因在早期上清刺激后增加。只有20个基因在耐药动物和易感动物之间存在差异表达，在控制感染方面没有明确的作用。总之，这表明MEC可能并不代表乳腺炎易感性差异起源的细胞类型，至少在我们的遗传模型中是这样。上清或热杀金黄色葡萄球菌产生的生物效应与活菌诱导的生物效应本质上不同。
Staphylococcus aureus is a prevalent pathogen for mastitis in dairy ruminants and is responsible for both clinical and subclinical mastitis. Mammary epithelial cells (MEC) represent not only a physical barrier against bacterial invasion but are also active players of the innate immune response permitting infection clearance. To decipher their functions in general and in animals showing different levels of genetic predisposition to Staphylococcus in particular, MEC from ewes undergoing a divergent selection on milk somatic cell count were stimulated by S. aureus. MEC response was also studied according to the stimulation condition with live bacteria or culture supernatant. The early MEC response was studied during a 5 h time course by microarray to identify differentially expressed genes with regard to the host genetic background and as a function of the conditions of stimulation. In both conditions of stimulation, metabolic processes were altered, the apoptosis-associated pathways were considerably modified, and inflammatory and immune responses were enhanced with the upregulation of il1a, il1b, and tnfa and several chemokines known to enhance neutrophil (cxcl8) or mononuclear leukocyte (ccl20) recruitment. Genes associated with oxidative stress were increased after live bacteria stimulation, whereas immune response-related genes were higher after supernatant stimulation in the early phase. Only 20 genes were differentially expressed between Staphylococcus spp-mastitis resistant and susceptible animals without any clearly defined role on the control of infection. To conclude, this suggests that MEC may not represent the cell type at the origin of the difference of mastitis susceptibility, at least as demonstrated in our genetic model. Supernatant or heat-killed S. aureus produce biological effects that are essentially different from those induced by live bacteria.