Borrelia burgdorferi induces a type I interferon response during early stages of disseminated infection in mice.

Borrelia burgdorferi induces a type I interferon response during early stages of disseminated infection in mice.
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DOI:
10.1186/s12866-016-0644-4
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发表时间:
2016-03-08
期刊:
影响因子:
4.2
通讯作者:
Schwartz I
Schwartz I
中科院分区:
生物学3区
文献类型:
--
作者:
Petzke MM;Iyer R;Love AC;Spieler Z;Brooks A;Schwartz I

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莱姆病疏螺旋体基因型在引起播散性疾病的能力上不同。采用基因阵列分析法分析了不同感染能力的伯氏疏螺旋体菌株在感染早期引起C3H/HeJ小鼠血液中播散性疾病的宿主转录组。B。在小鼠中引起播散性感染的临床分离物burgdorferiB515差异调节236个转录物(通过ANOVA,P <0.05,倍数变化至少为2)。216个显著诱导的转录本包括干扰素(IFN)应答基因和免疫和炎症相关基因。相反,B. burgdorferiB331是一种引起短暂皮肤感染但在C3H/HeJ小鼠中不传播的临床分离株,其仅刺激少数基因的变化(1个诱导,4个抑制)。在用B接种后24小时从感染部位收集的小鼠皮肤活检中,通过定量RT-PCR测量I型IFN和IFN相关基因的转录调节。burgdorferi。在B中发现Ifnb、Cxcl10、Gbp 1、Ifit 1、Ifit 3、Irf 7、Mx 1和Stat2的转录物的平均值显著增加。与对照组相比,Burgdorferi菌株B515感染的小鼠。相反,这些基因的转录没有显着改变响应B。Burgdorferi菌株B331或B31 - 4,不能传播的突变体。这些结果建立了B的传播能力之间的正相关。莱姆病小鼠模型中的伯氏螺旋体和早期I型IFN诱导。
Lyme borrelia genotypes differ in their capacity to cause disseminated disease. Gene array analysis was employed to profile the host transcriptome induced by Borrelia burgdorferi strains with different capacities for causing disseminated disease in the blood of C3H/HeJ mice during early infection. B. burgdorferi B515, a clinical isolate that causes disseminated infection in mice, differentially regulated 236 transcripts (P < 0.05 by ANOVA, with fold change of at least 2). The 216 significantly induced transcripts included interferon (IFN)-responsive genes and genes involved in immunity and inflammation. In contrast, B. burgdorferi B331, a clinical isolate that causes transient skin infection but does not disseminate in C3H/HeJ mice, stimulated changes in only a few genes (1 induced, 4 repressed). Transcriptional regulation of type I IFN and IFN-related genes was measured by quantitative RT-PCR in mouse skin biopsies collected from the site of infection 24 h after inoculation with B. burgdorferi. The mean values for transcripts of Ifnb, Cxcl10, Gbp1, Ifit1, Ifit3, Irf7, Mx1, and Stat2 were found to be significantly increased in B. burgdorferi strain B515-infected mice relative to the control group. In contrast, transcription of these genes was not significantly changed in response to B. burgdorferi strain B331 or B31-4, a mutant that is unable to disseminate. These results establish a positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction in a murine model of Lyme disease.