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大肠杆菌感染诱导乳腺中独特的局部和全身转录组反应。

Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland.

机构信息

Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str 25, 81377 Munich, Germany.

出版信息

BMC Genomics. 2010 Feb 25;11:138. doi: 10.1186/1471-2164-11-138.

Abstract

BACKGROUND

Coliform bacteria are the most common etiologic agents in severe mastitis of cows. Escherichia coli infections are mostly restricted to a single udder quarter whereas neighboring quarters stay clinically inapparent, implicating the presence of a systemic defense reaction. To address its underlying mechanism, we performed a transcriptome study of mammary tissue from udder quarters inoculated with E. coli (6 h and 24 h post infection), from neighboring quarters of the same animals, and from untreated control animals.

RESULTS

After 6 h 13 probe sets of differentially expressed genes (DEG) were detected in infected quarters versus control animals. Eighteen hours later 2154 and 476 DEG were found in infected and in neighboring quarters vs. control animals. Cluster analysis revealed DEG found only in infected quarters (local response) and DEG detected in both infected and neighboring quarters (systemic response). The first group includes genes mainly involved in immune response and inflammation, while the systemic reaction comprises antigen processing and presentation, cytokines, protein degradation and apoptosis. Enhanced expression of antimicrobial genes (S100A8, S100A9, S100A12, CXCL2, GNLY), acute phase genes (LBP, SAA3, CP, BF, C6, C4BPA, IF), and indicators of oxidative stress (GPX3, MT1A, MT2A, SOD2) point to an active defense reaction in infected and neighboring healthy quarters. Its early onset is indicated by increased transcription of NFIL3 at 6 h. NFIL3 is a predicted regulator of many genes of the systemic response at 24 h. The significance of our transcriptome study was evidenced by some recent findings with candidate gene based approaches.

CONCLUSIONS

The discovery and holistic analysis of an extensive systemic reaction in the mammary gland significantly expands the knowledge of host-pathogen interactions in mastitis which may be relevant for the development of novel therapies and for genetic selection towards mastitis resistance.

摘要

背景

大肠埃希菌是奶牛严重乳腺炎最常见的病原体。大肠杆菌感染大多局限于单个乳区,而相邻的乳区在临床上没有明显的症状,这表明存在全身性防御反应。为了探讨其潜在机制,我们对感染大肠杆菌(感染后 6 小时和 24 小时)的乳区、同一动物相邻乳区和未处理对照动物的乳腺组织进行了转录组研究。

结果

感染后 6 小时,感染乳区与对照动物相比有 13 个差异表达基因(DEG)探针集被检测到。18 小时后,感染和相邻乳区与对照动物相比分别发现了 2154 和 476 个 DEG。聚类分析显示,仅在感染乳区发现的 DEG(局部反应)和在感染和相邻乳区均发现的 DEG(全身反应)。第一组包括主要参与免疫反应和炎症的基因,而全身反应包括抗原加工和呈递、细胞因子、蛋白质降解和细胞凋亡。抗菌基因(S100A8、S100A9、S100A12、CXCL2、GNLY)、急性期基因(LBP、SAA3、CP、BF、C6、C4BPA、IF)和氧化应激标志物(GPX3、MT1A、MT2A、SOD2)的表达增强表明感染和相邻健康乳区存在活跃的防御反应。NFIL3 在 6 小时时的转录增加表明其早期发生。NFIL3 是 24 小时全身反应中许多基因的预测调节因子。基于候选基因的方法的一些最新发现证明了我们的转录组研究的意义。

结论

在乳腺中发现并全面分析广泛的全身反应显著扩展了乳腺炎中宿主-病原体相互作用的知识,这可能与新型疗法的开发和乳腺炎抗性的遗传选择有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d6f/2846913/d908cbe87802/1471-2164-11-138-1.jpg

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