Induction of Type I and Type III Interferons by Borrelia burgdorferi Correlates with Pathogenesis and Requires Linear Plasmid 36
Induction of Type I and Type III Interferons by Borrelia burgdorferi Correlates with Pathogenesis and Requires Linear Plasmid 36
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DOI：
10.1371/journal.pone.0100174
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发表时间：
2014-06-19
期刊：
影响因子：
3.7
通讯作者：
Petzke, Mary M.
中科院分区：
文献类型：
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作者：
Krupna-Gaylord, Michelle A.;Liveris, Dionysios;Petzke, Mary M.
伯氏疏螺旋体在人类或小鼠中引起播散性感染的能力与感染菌株的基因型相关。由B引起的细胞因子谱。在人PBMC共孵育模型中评估不同基因型（核糖体间隔区类型）组的伯氏临床分离株。与人类和小鼠中的播散性莱姆病更频繁相关的RST 1分离株相对于与播散性感染不太频繁相关的RST 3分离株诱导显著更高水平的IFN-α和IFN-λ/IL 29。在不同基因型的分离株之间没有观察到IFN-γ、IL-1 β、IL-6、IL-8、IL-10或TNF-α的蛋白浓度的差异。B的能力。burgdorferi诱导I型和III型IFN的能力完全依赖于线性质粒（lp）36的存在。一个lp 36缺陷型B。与其同基因B31亲本菌株相比，Burgdorferi突变体粘附于PBMC和特异性树突状细胞（DC）亚群并被其内化的效率较低。与mDC 1 s和pDC的关联缺陷可以通过用完整的lp 36互补突变体来恢复。研究的RST 1临床分离株发现含有一个2.5 kB区域，位于lp 36的远端三分之一，这在任何测试的RST 3分离株中都不存在。lp 36的这个趋异区可能编码一个或多个因子，这些因子是最佳螺旋体识别和人DC产生I型和III型IFN所需的，因此表明DC在B发病机制中的潜在作用。伯氏感染
The capacity for Borrelia burgdorferi to cause disseminated infection in humans or mice is associated with the genotype of the infecting strain. The cytokine profiles elicited by B. burgdorferi clinical isolates of different genotype (ribosomal spacer type) groups were assessed in a human PBMC co-incubation model. RST1 isolates, which are more frequently associated with disseminated Lyme disease in humans and mice, induced significantly higher levels of IFN-alpha and IFN-lambda/IL29 relative to RST3 isolates, which are less frequently associated with disseminated infection. No differences in the protein concentrations of IFN-gamma, IL-1 beta, IL-6, IL-8, IL-10 or TNF-alpha were observed between isolates of differing genotype. The ability of B. burgdorferi to induce type I and type III IFNs was completely dependent on the presence of linear plasmid (lp) 36. An lp36-deficient B. burgdorferi mutant adhered to, and was internalized by, PBMCs and specific dendritic cell (DC) subsets less efficiently than its isogenic B31 parent strain. The association defect with mDC1s and pDCs could be restored by complementation of the mutant with the complete lp36. The RST1 clinical isolates studied were found to contain a 2.5-kB region, located in the distal one-third of lp36, which was not present in any of the RST3 isolates tested. This divergent region of lp36 may encode one or more factors required for optimal spirochetal recognition and the production of type I and type III IFNs by human DCs, thus suggesting a potential role for DCs in the pathogenesis of B. burgdorferi infection.