Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine Macrophages

Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most prevalent vector-borne disease in the United States. Macrophages, key cellular players in the innate immune response, exhibit diminished functionality over time during Bb infection, potentially leading to chronic infectio...

Full description

Saved in:
Bibliographic Details
Main Authors: Sophia Chen, Ricki Deng, Anis Hadi, Sara Nandwana, William Ryan, John B. Presloid, R. Mark Wooten
Format: Article
Language:English
Published: The University of Toledo 2025-02-01
Series:Translation
Subjects:
Online Access:https://openjournals.utoledo.edu/index.php/translation/article/view/1536
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832095374343405568
author Sophia Chen
Ricki Deng
Anis Hadi
Sara Nandwana
William Ryan
John B. Presloid
R. Mark Wooten
author_facet Sophia Chen
Ricki Deng
Anis Hadi
Sara Nandwana
William Ryan
John B. Presloid
R. Mark Wooten
author_sort Sophia Chen
collection DOAJ
description Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most prevalent vector-borne disease in the United States. Macrophages, key cellular players in the innate immune response, exhibit diminished functionality over time during Bb infection, potentially leading to chronic infection. This study explores the transcriptional changes associated with macrophages that develop tolerance to Bb. Using RNA sequencing of murine bone marrow-derived macrophages exposed to Bb, we identified differentially expressed genes and dysregulated pathways between productively stimulated and tolerized macrophages. Key findings revealed significant downregulation of type-I interferon signaling and associated immune responses, suggesting mechanisms of immune tolerance. Additionally, connectivity analysis identified potential drug candidates for repurposing to enhance macrophage activity. Our results underscore the complexity of macrophage responses to Bb and provide a foundation for future research to develop targeted therapies aimed at modulating immune responses and improving treatment outcomes for Lyme disease patients. Ultimately, these findings offer new insights into the pathogenesis and potential treatment strategies for Lyme disease.
format Article
id doaj-art-060d33c83e3242bfb43bc65b2336572d
institution Kabale University
issn 2469-6706
language English
publishDate 2025-02-01
publisher The University of Toledo
record_format Article
series Translation
spelling doaj-art-060d33c83e3242bfb43bc65b2336572d2025-02-05T18:17:54ZengThe University of ToledoTranslation2469-67062025-02-0113S110.46570/utjms-2025-1536Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine MacrophagesSophia ChenRicki DengAnis HadiSara NandwanaWilliam Ryan0John B. PresloidR. Mark WootenUT COMLS Lyme disease, caused by the spirochete Borrelia burgdorferi (Bb), is the most prevalent vector-borne disease in the United States. Macrophages, key cellular players in the innate immune response, exhibit diminished functionality over time during Bb infection, potentially leading to chronic infection. This study explores the transcriptional changes associated with macrophages that develop tolerance to Bb. Using RNA sequencing of murine bone marrow-derived macrophages exposed to Bb, we identified differentially expressed genes and dysregulated pathways between productively stimulated and tolerized macrophages. Key findings revealed significant downregulation of type-I interferon signaling and associated immune responses, suggesting mechanisms of immune tolerance. Additionally, connectivity analysis identified potential drug candidates for repurposing to enhance macrophage activity. Our results underscore the complexity of macrophage responses to Bb and provide a foundation for future research to develop targeted therapies aimed at modulating immune responses and improving treatment outcomes for Lyme disease patients. Ultimately, these findings offer new insights into the pathogenesis and potential treatment strategies for Lyme disease. https://openjournals.utoledo.edu/index.php/translation/article/view/1536Borrelia burgdorferiLyme diseasemacrophagetolerancetranscriptional profilingdrug discovery
spellingShingle Sophia Chen
Ricki Deng
Anis Hadi
Sara Nandwana
William Ryan
John B. Presloid
R. Mark Wooten
Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine Macrophages
Translation
Borrelia burgdorferi
Lyme disease
macrophage
tolerance
transcriptional profiling
drug discovery
title Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine Macrophages
title_full Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine Macrophages
title_fullStr Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine Macrophages
title_full_unstemmed Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine Macrophages
title_short Borrelia burgdorferi Tolerance-Associated Changes in Gene Expression of Murine Macrophages
title_sort borrelia burgdorferi tolerance associated changes in gene expression of murine macrophages
topic Borrelia burgdorferi
Lyme disease
macrophage
tolerance
transcriptional profiling
drug discovery
url https://openjournals.utoledo.edu/index.php/translation/article/view/1536
work_keys_str_mv AT sophiachen borreliaburgdorferitoleranceassociatedchangesingeneexpressionofmurinemacrophages
AT rickideng borreliaburgdorferitoleranceassociatedchangesingeneexpressionofmurinemacrophages
AT anishadi borreliaburgdorferitoleranceassociatedchangesingeneexpressionofmurinemacrophages
AT saranandwana borreliaburgdorferitoleranceassociatedchangesingeneexpressionofmurinemacrophages
AT williamryan borreliaburgdorferitoleranceassociatedchangesingeneexpressionofmurinemacrophages
AT johnbpresloid borreliaburgdorferitoleranceassociatedchangesingeneexpressionofmurinemacrophages
AT rmarkwooten borreliaburgdorferitoleranceassociatedchangesingeneexpressionofmurinemacrophages