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AxBioTick研究——感染伯氏疏螺旋体与未感染蜱虫叮咬的人体皮肤中的免疫基因表达特征。

The AxBioTick study - immune gene expression signatures in human skin bitten by Borrelia-infected versus non-infected ticks.

作者信息

Berthén Nellie Carlströmer, Cronhjort Samuel, Nordberg Marika, Lindgren Per-Eric, Larsson Marie, Wilhelmsson Peter, Sjöwall Johanna

机构信息

The Borrelia Research Group of the Åland Islands, the Åland Islands, Mariehamn, Finland.

Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

出版信息

BMC Infect Dis. 2024 Dec 18;24(1):1422. doi: 10.1186/s12879-024-10279-2.

DOI:10.1186/s12879-024-10279-2
PMID:39695466
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11654342/
Abstract

BACKGROUND

Borrelia infection is caused by Borrelia burgdorferi sensu lato and transmitted by Ixodes ricinus ticks, a common tick-borne infection in Northern Europe. The establishment of Borrelia infection depends on transmission of the spirochetes, as well as the immune response generated in the skin after a bite. Here we aim to investigate the local immune response in the skin after a tick bite and assess the possible direct effects of Borrelia, by applying gene expression analysis of the immune response in skin exposed to Borrelia-infected and non-infected ticks, respectively.

METHODS

Skin biopsies from the study participants were taken 7-10 days after the tick-bite. The ticks and skin biopsies were analysed by real-time PCR for Borrelia spp. and other tick-borne pathogens. Dermal transcriptome profiles derived from RNA sequencing with focus on immune system regulation were created. In addition, we performed enrichment analysis of dermal transcriptome profiles with focus on immune system regulation.

RESULTS

Skin biopsies exposed to a Borrelia-positive tick induced an overall higher expression of immune-related genes. Cytokines involved in the regulation of T-cell and macrophage activation, pro-inflammatory regulators and Toll-like receptor 2, 3 and 7 involved in pathogen recognition were upregulated in skin exposed to Borrelia, although Borrelia DNA was not detected in the biopsies.

CONCLUSION

The evidence of upregulation of genes in Borrelia exposed skin suggests an influence on the immune system of ticks and spirochetes. Characterization of Borrelia-associated gene expression signatures in the skin could contribute to future diagnostics and increase our understanding of the development of various manifestations of Borrelia infection.

摘要

背景

伯氏疏螺旋体感染由广义伯氏疏螺旋体引起,通过蓖麻硬蜱传播,是北欧常见的蜱传感染。伯氏疏螺旋体感染的建立取决于螺旋体的传播以及叮咬后皮肤中产生的免疫反应。在此,我们旨在通过分别对暴露于感染伯氏疏螺旋体和未感染伯氏疏螺旋体的蜱的皮肤中的免疫反应进行基因表达分析,来研究蜱叮咬后皮肤中的局部免疫反应,并评估伯氏疏螺旋体可能的直接作用。

方法

在蜱叮咬后7 - 10天采集研究参与者的皮肤活检样本。通过实时PCR对蜱和皮肤活检样本进行伯氏疏螺旋体属及其他蜱传病原体分析。创建了侧重于免疫系统调节的RNA测序衍生的真皮转录组图谱。此外,我们对侧重于免疫系统调节的真皮转录组图谱进行了富集分析。

结果

暴露于伯氏疏螺旋体阳性蜱的皮肤活检样本诱导了免疫相关基因的整体更高表达。尽管在活检样本中未检测到伯氏疏螺旋体DNA,但在暴露于伯氏疏螺旋体的皮肤中,参与T细胞和巨噬细胞激活调节的细胞因子、促炎调节因子以及参与病原体识别的Toll样受体2、3和7均上调。

结论

暴露于伯氏疏螺旋体的皮肤中基因上调的证据表明蜱和螺旋体对免疫系统有影响。皮肤中伯氏疏螺旋体相关基因表达特征的表征可能有助于未来的诊断,并增进我们对伯氏疏螺旋体感染各种表现形式发展的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/562a0bb62b79/12879_2024_10279_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/8f441b89b669/12879_2024_10279_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/3c05b977546a/12879_2024_10279_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/9b9cc94a1a16/12879_2024_10279_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/562a0bb62b79/12879_2024_10279_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/8f441b89b669/12879_2024_10279_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/3c05b977546a/12879_2024_10279_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/9b9cc94a1a16/12879_2024_10279_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4546/11654342/562a0bb62b79/12879_2024_10279_Fig4_HTML.jpg

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