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大软骨蛋白聚糖基因敲除小鼠的伯氏疏螺旋体感染。

Borrelia burgdorferi Infection in Biglycan Knockout Mice.

机构信息

Institute of Biomedicine, University of Turku.

Turku Doctoral Programme of Molecular Medicine, Faculty of Medicine, University of Turku.

出版信息

J Infect Dis. 2019 Jun 5;220(1):116-126. doi: 10.1093/infdis/jiz050.

Abstract

BACKGROUND

Borrelia burgdorferi sensu lato spirochetes (Borrelia) causing Lyme borreliosis are able to disseminate from the initial entry site to distant organs in the host. Outer-surface adhesins are crucial in the bacterial dissemination and adhesion to various tissues. Two well-characterized Borrelia adhesins, decorin-binding proteins A and B, have been shown to bind to 2 host receptors, decorin and biglycan. However, the role of biglycan in Borrelia infection has not been characterized in vivo.

METHODS

We infected biglycan knockout (KO) and wild-type (WT) C3H mice with strains representing 3 Borrelia genospecies, Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. The infection was monitored by measuring joint swelling, Borrelia culture, polymerase chain reaction analysis, and serologic analysis. The host immune responses were analyzed by histological scoring of the inflammation in tissues and by cytokine profiling.

RESULTS

B. burgdorferi sensu stricto and B. garinii established long-term infection in mice of both genotypes, while B. afzelii failed to disseminate in KO mice. Further, the B. burgdorferi sensu stricto-infected KO mice had persistent inflammation in the joints.

CONCLUSIONS

The dissemination and tissue colonization of Borrelia and the inflammatory response of the host differ in a mouse biglycan expression- and Borrelia genospecies-dependent manner.

摘要

背景

导致莱姆病的伯氏疏螺旋体(Borrelia)能够从初始进入部位传播到宿主的远处器官。表面黏附素对于细菌的传播和黏附到各种组织至关重要。两种经过充分研究的伯氏疏螺旋体黏附素,即整联蛋白结合蛋白 A 和 B,已被证明可以结合 2 种宿主受体,即decorin 和 biglycan。然而,biglycan 在伯氏疏螺旋体感染中的作用尚未在体内进行表征。

方法

我们用代表 3 种伯氏疏螺旋体种的菌株感染 biglycan 敲除(KO)和野生型(WT)C3H 小鼠,即伯氏疏螺旋体 sensu stricto、伯氏疏螺旋体 garinii 和伯氏疏螺旋体 afzelii。通过测量关节肿胀、Borrelia 培养、聚合酶链反应分析和血清学分析来监测感染。通过组织炎症的组织学评分和细胞因子谱分析来分析宿主免疫反应。

结果

B. burgdorferi sensu stricto 和 B. garinii 在两种基因型的小鼠中均建立了长期感染,而 B. afzelii 未能在 KO 小鼠中传播。此外,B. burgdorferi sensu stricto 感染的 KO 小鼠关节持续存在炎症。

结论

Borrelia 的传播和组织定植以及宿主的炎症反应在依赖于小鼠 biglycan 表达和 Borrelia 种的方式上有所不同。

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