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首页> 外文期刊>Infection and immunity >Liver Transcriptome Profiles Associated with Strain-Specific Ehrlichia chaffeensis-Induced Hepatitis in SCID Mice
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Liver Transcriptome Profiles Associated with Strain-Specific Ehrlichia chaffeensis-Induced Hepatitis in SCID Mice

机译:与SCID小鼠特定菌株恰菲埃里希氏菌引起的肝炎相关的肝转录组谱

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Infection of humans with Ehrlichia chaffeensis, the etiologic agent of human monocytic ehrlichiosis, can cause hepatitis of various levels of severity. When the three human isolates of E. chaffeensis, each belonging to a different genogroup, are inoculated into severe combined immunodeficiency mice, the order of severity of clinical signs and bacterial burden detected in the liver is as follows (from greatest to least severity and highest to lowest burden): strain Wakulla, followed by strain Liberty, followed by strain Arkansas. In this article, we used microarray analysis to define transcriptional profiles characteristic of the histopathological features in the mouse liver. Cytokine and chemokine profiles and their receptor profiles were strikingly different among the three strains of E. chaffeensis: gamma interferon, CCL5, CXCL1, CXCL2, CXCL7, CXCL9, interleukin 2 receptor gamma (IL2Rγ), IL21R, CCR2, and CXCR6 were highly upregulated with strain Arkansas; and tumor necrosis factor (TNF), CCL2, CCL3, CCL5, CCL6, CCL12, CCL20, CXCL2, CXCL7, CXCL9, CXCL13, TNF receptor superfamily 9 (TNFRSF9), TNFRSF13β, IL1R2, IL2Rγ, IL20Rβ, IL21R, CCR1, CCR2, and CXCR4 were highly upregulated with strain Wakulla. With strain Liberty, only CXCL13 was highly upregulated, and IL13Rα2 was downregulated. In livers infected with the Arkansas strain, monocytes/macrophages and NK cells were enriched in the granulomas and an increase in NK cell marker mRNAs was detected. Livers infected with the Wakulla strain displayed infiltration of significantly more neutrophils and an increase in neutrophil marker mRNAs. Genes commonly upregulated in liver tissue infected with the three strains are other host innate immune and inflammatory response genes, including those encoding several acute-phase proteins. Genes downregulated commonly are related to host physiologic functions. The results suggest that marked modulation of host cytokine and chemokine profiles by E. chaffeensis strains underlies the distinct host liver disease.
机译:感染人单核细胞埃希氏菌病的病原体 Ehrlichia chaffeensis 会导致各种程度的肝炎。当三个人类分离的 E。 Chaffeensis (分别属于不同的基因组)被接种到严重的联合免疫缺陷小鼠中,在肝脏中检测到的临床体征和细菌负荷的严重程度如下(从最大到最小,从最大到最小) :Wakulla菌株,然后是Liberty菌株,然后是Arkansas菌株。在本文中,我们使用微阵列分析来定义小鼠肝脏组织病理学特征的转录特征。在三个 E菌株中,细胞因子和趋化因子谱及其受体谱显着不同。 chaffeensis :阿肯色菌株对γ-干扰素,CCL5,CXCL1,CXCL2,CXCL7,CXCL9,白介素2受体γ(IL2Rγ),IL21R,CCR2和CXCR6高度上调。和肿瘤坏死因子(TNF),CCL2,CCL3,CCL5,CCL6,CCL12,CCL20,CXCL2,CXCL7,CXCL9,CXCL13,TNF受体超家族9(TNFRSF9),TNFRSF13β,IL1R2,IL2Rγ,IL20Rβ,IL21R,CCR Wakulla菌株对CXCR4和CXCR4高度上调。对于Liberty菌株,仅CXCL13上调,而IL13Rα2下调。在感染了阿肯色菌株的肝脏中,肉芽肿中富含单核细胞/巨噬细胞和NK细胞,并且检测到NK细胞标记物mRNA的增加。感染了Wakulla菌株的肝脏表现出明显更多的中性粒细胞浸润和中性粒细胞标志物mRNA的增加。在感染了这三株病毒的肝组织中通常上调的基因是其他宿主固有的免疫和炎症反应基因,包括那些编码几种急性期蛋白的基因。通常被下调的基因与宿主的生理功能有关。结果表明, E对宿主细胞因子和趋化因子谱的显着调节。 Chaffeensis 菌株是独特的宿主肝病的基础。

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