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

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...

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Main Authors: Nellie Carlströmer Berthén, Samuel Cronhjort, Marika Nordberg, Per-Eric Lindgren, Marie Larsson, Peter Wilhelmsson, Johanna Sjöwall
Format: Article
Language:English
Published: BMC 2024-12-01
Series:BMC Infectious Diseases
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Online Access:https://doi.org/10.1186/s12879-024-10279-2
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author Nellie Carlströmer Berthén
Samuel Cronhjort
Marika Nordberg
Per-Eric Lindgren
Marie Larsson
Peter Wilhelmsson
Johanna Sjöwall
author_facet Nellie Carlströmer Berthén
Samuel Cronhjort
Marika Nordberg
Per-Eric Lindgren
Marie Larsson
Peter Wilhelmsson
Johanna Sjöwall
author_sort Nellie Carlströmer Berthén
collection DOAJ
description 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.
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spelling doaj-art-b39bada9fc7f46c799cdc6fb6d2e428e2024-12-22T12:17:29ZengBMCBMC Infectious Diseases1471-23342024-12-0124111110.1186/s12879-024-10279-2The AxBioTick study – immune gene expression signatures in human skin bitten by Borrelia-infected versus non-infected ticksNellie Carlströmer Berthén0Samuel Cronhjort1Marika Nordberg2Per-Eric Lindgren3Marie Larsson4Peter Wilhelmsson5Johanna Sjöwall6The Borrelia Research Group of the Åland IslandsDivision of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping UniversityThe Borrelia Research Group of the Åland IslandsDivision of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping UniversityDivision of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping UniversityDivision of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping UniversityDivision of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping UniversityAbstract 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.https://doi.org/10.1186/s12879-024-10279-2SkinHumanTick biteBorreliaImmune responseTranscriptome
spellingShingle Nellie Carlströmer Berthén
Samuel Cronhjort
Marika Nordberg
Per-Eric Lindgren
Marie Larsson
Peter Wilhelmsson
Johanna Sjöwall
The AxBioTick study – immune gene expression signatures in human skin bitten by Borrelia-infected versus non-infected ticks
BMC Infectious Diseases
Skin
Human
Tick bite
Borrelia
Immune response
Transcriptome
title The AxBioTick study – immune gene expression signatures in human skin bitten by Borrelia-infected versus non-infected ticks
title_full The AxBioTick study – immune gene expression signatures in human skin bitten by Borrelia-infected versus non-infected ticks
title_fullStr The AxBioTick study – immune gene expression signatures in human skin bitten by Borrelia-infected versus non-infected ticks
title_full_unstemmed The AxBioTick study – immune gene expression signatures in human skin bitten by Borrelia-infected versus non-infected ticks
title_short The AxBioTick study – immune gene expression signatures in human skin bitten by Borrelia-infected versus non-infected ticks
title_sort axbiotick study immune gene expression signatures in human skin bitten by borrelia infected versus non infected ticks
topic Skin
Human
Tick bite
Borrelia
Immune response
Transcriptome
url https://doi.org/10.1186/s12879-024-10279-2
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