Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infection

Summary: Lyme disease is caused by the bacterial pathogen Borrelia burgdorferi, which can be readily modeled in laboratory mice. In order to understand the cellular and transcriptional changes that occur during B. burgdorferi infection, we conducted single-cell RNA sequencing (scRNA-seq) of ankle jo...

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Main Authors: Jennifer D. Helble, Michael J. Walsh, Julie E. McCarthy, Neal P. Smith, Alice J. Tirard, Benjamin Y. Arnold, Alexandra-Chloe Villani, Linden T. Hu
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223022940
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author Jennifer D. Helble
Michael J. Walsh
Julie E. McCarthy
Neal P. Smith
Alice J. Tirard
Benjamin Y. Arnold
Alexandra-Chloe Villani
Linden T. Hu
author_facet Jennifer D. Helble
Michael J. Walsh
Julie E. McCarthy
Neal P. Smith
Alice J. Tirard
Benjamin Y. Arnold
Alexandra-Chloe Villani
Linden T. Hu
author_sort Jennifer D. Helble
collection DOAJ
description Summary: Lyme disease is caused by the bacterial pathogen Borrelia burgdorferi, which can be readily modeled in laboratory mice. In order to understand the cellular and transcriptional changes that occur during B. burgdorferi infection, we conducted single-cell RNA sequencing (scRNA-seq) of ankle joints of infected C57BL/6 mice over time. We found that macrophages/monocytes, T cells, synoviocytes and fibroblasts all showed significant differences in gene expression of both inflammatory and non-inflammatory genes that peaked early and returned to baseline before the typical resolution of arthritis. Predictions of cellular interactions showed that macrophages appear to communicate extensively between different clusters of macrophages as well as with fibroblasts and synoviocytes. Our data give unique insights into the interactions between B. burgdorferi and the murine immune system over time and allow for a better understanding of mechanisms by which the dysregulation of the immune response may lead to prolonged symptoms in some patients.
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spelling doaj.art-d6183220150540f2ace8e1063c19b3252023-10-27T04:24:34ZengElsevieriScience2589-00422023-11-012611108217Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infectionJennifer D. Helble0Michael J. Walsh1Julie E. McCarthy2Neal P. Smith3Alice J. Tirard4Benjamin Y. Arnold5Alexandra-Chloe Villani6Linden T. Hu7Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USADivision of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Cancer Immunology and Virology, Dana Farber Cancer Institute, Boston, MA 02215, USADepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USADepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USADepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USADepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USADepartment of Medicine, Massachusetts General Hospital, Boston, MA 02114, USADepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA; Corresponding authorSummary: Lyme disease is caused by the bacterial pathogen Borrelia burgdorferi, which can be readily modeled in laboratory mice. In order to understand the cellular and transcriptional changes that occur during B. burgdorferi infection, we conducted single-cell RNA sequencing (scRNA-seq) of ankle joints of infected C57BL/6 mice over time. We found that macrophages/monocytes, T cells, synoviocytes and fibroblasts all showed significant differences in gene expression of both inflammatory and non-inflammatory genes that peaked early and returned to baseline before the typical resolution of arthritis. Predictions of cellular interactions showed that macrophages appear to communicate extensively between different clusters of macrophages as well as with fibroblasts and synoviocytes. Our data give unique insights into the interactions between B. burgdorferi and the murine immune system over time and allow for a better understanding of mechanisms by which the dysregulation of the immune response may lead to prolonged symptoms in some patients.http://www.sciencedirect.com/science/article/pii/S2589004223022940ImmunologyMicrobiologyCell biologyTranscriptomics
spellingShingle Jennifer D. Helble
Michael J. Walsh
Julie E. McCarthy
Neal P. Smith
Alice J. Tirard
Benjamin Y. Arnold
Alexandra-Chloe Villani
Linden T. Hu
Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infection
iScience
Immunology
Microbiology
Cell biology
Transcriptomics
title Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infection
title_full Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infection
title_fullStr Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infection
title_full_unstemmed Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infection
title_short Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infection
title_sort single cell rna sequencing of murine ankle joints over time reveals distinct transcriptional changes following borrelia burgdorferi infection
topic Immunology
Microbiology
Cell biology
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004223022940
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