Petzke Mary M, Iyer Radha, Love Andrea C, Spieler Zoe, Brooks Andrew, Schwartz Ira
Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA.
Present Address: Nexcelom Bioscience LLC, Lawrence, Massachusetts, USA.
BMC Microbiol. 2016 Mar 8;16:29. doi: 10.1186/s12866-016-0644-4.
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.
莱姆疏螺旋体基因型在引起播散性疾病的能力上存在差异。采用基因芯片分析技术,对感染初期不同播散能力的伯氏疏螺旋体菌株在C3H/HeJ小鼠血液中诱导的宿主转录组进行分析。
能在小鼠中引起播散性感染的临床分离株伯氏疏螺旋体B515,差异调节了236个转录本(经方差分析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)反应基因以及参与免疫和炎症的基因。相比之下,能引起短暂皮肤感染但在C3H/HeJ小鼠中不播散的临床分离株伯氏疏螺旋体B331,仅刺激了少数基因的变化(1个诱导,4个抑制)。接种伯氏疏螺旋体24小时后,通过定量逆转录聚合酶链反应(RT-PCR)检测小鼠皮肤活检样本中I型干扰素和IFN相关基因的转录调控。发现伯氏疏螺旋体B515感染小鼠中Ifnb、Cxcl10、Gbp1、Ifit1、Ifit3、Irf7、Mx1和Stat2转录本的平均值相对于对照组显著增加。相比之下,这些基因的转录在伯氏疏螺旋体B331或无法播散的突变株B31 - 4刺激下没有显著变化。
这些结果在莱姆病小鼠模型中建立了伯氏疏螺旋体的播散能力与早期I型干扰素诱导之间的正相关关系。