Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry

  1. Kimberley RG Cortenbach
  2. Alexander HJ Staal
  3. Teske Schoffelen
  4. Mark AJ Gorris
  5. Lieke L Van der Woude
  6. Anne FM Jansen
  7. Paul Poyck
  8. Robert Jan Van Suylen
  9. Peter C Wever
  10. Chantal P Bleeker-Rovers
  11. Mangala Srinivas
  12. Konnie M Hebeda
  13. Marcel van Deuren
  14. Jos W Van der Meer
  15. Jolanda M De Vries
  16. Roland RJ Van Kimmenade  Is a corresponding author
  1. Radboud Institute for Molecular Life Sciences, Netherlands
  2. Radboud University Medical Centre, Netherlands
  3. Jeroen Bosch Ziekenhuis, Netherlands
  4. Radboud University Medical Center, Netherlands

Abstract

Background: Chronic Q fever is a zoonosis caused by the bacterium Coxiella burnetii which can manifest as infection of an abdominal aortic aneurysm (AAA). Antibiotic therapy often fails, resulting in severe morbidity and high mortality. Whereas previous studies have focused on inflammatory processes in blood, the aim of this study was to investigate local inflammation in aortic tissue.

Methods: Multiplex immunohistochemistry was used to investigate local inflammation in Q fever AAAs compared to atherosclerotic AAAs in aorta tissue specimen. Two six-plex panels were used to study both the innate and adaptive immune system.

Results: Q fever AAAs and atherosclerotic AAAs contained similar numbers of CD68+ macrophages and CD3+ T cells. However, in Q fever AAAs the number of CD68+CD206+ M2 macrophages was increased, while expression of GM-CSF was decreased compared to atherosclerotic AAAs. Furthermore, Q fever AAAs showed an increase in both the number of CD8+ cytotoxic T cells and CD3+CD8-FoxP3+ regulatory T cells. Lastly, Q fever AAAs did not contain any well-defined granulomas.

Conclusions: These findings demonstrate that despite the presence of pro-i is associated with an immune suppressed micro environment.

Funding: This work was supported by SCAN consortium: European Research Area - CardioVascualar Diseases (ERA-CVD) grant [JTC2017-044] and TTW-NWO open technology grant [STW-14716].

Data availability

All data generated or analyzed during this study are included in the manuscript and uploaded to Dryad (http://dx.doi.org/10.5061/dryad.bzkh189b4).Figure 3 - Source data 3; Figure 5 - Source data 5; Figure 6 - Source figure 6; Figure 7 - Source figure 7 contain numerical data used to generate the figures.

The following data sets were generated
    1. Cortenbach KR
    (2021) Vascular Q fever inflammation
    Dryad Digital Repository, doi:10.5061/dryad.bzkh189b4.

Article and author information

Author details

  1. Kimberley RG Cortenbach

    Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2717-5527
  2. Alexander HJ Staal

    Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  3. Teske Schoffelen

    Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  4. Mark AJ Gorris

    Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  5. Lieke L Van der Woude

    Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  6. Anne FM Jansen

    Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  7. Paul Poyck

    Department of Surgery, Radboud University Medical Centre, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  8. Robert Jan Van Suylen

    Department of Pathology, Jeroen Bosch Ziekenhuis, 's Hertogenbosch, Netherlands
    Competing interests
    No competing interests declared.
  9. Peter C Wever

    Department of Medical Microbiology and Infection Control, Jeroen Bosch Ziekenhuis, 's Hertogenbosch, Netherlands
    Competing interests
    No competing interests declared.
  10. Chantal P Bleeker-Rovers

    Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  11. Mangala Srinivas

    Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  12. Konnie M Hebeda

    Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4181-3302
  13. Marcel van Deuren

    Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  14. Jos W Van der Meer

    Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands
    Competing interests
    Jos W Van der Meer, Senior editor, eLife.
  15. Jolanda M De Vries

    Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands
    Competing interests
    No competing interests declared.
  16. Roland RJ Van Kimmenade

    Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands
    For correspondence
    Roland.vanKimmenade@radboudumc.nl
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8207-8906

Funding

European Research Area - Cardiovascular Diseases (JTC2017-044)

  • Kimberley RG Cortenbach

TTW-NWO Open Technology (STW-14716)

  • Alexander HJ Staal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Christina L Stallings, Washington University School of Medicine, United States

Ethics

Human subjects: The medical ethics committees of the institutions approved the study, in line with the principlesoutlined in the Declaration of Helsinki (Radboudumc: 2017-3196; Jeroen Bosch Hospital:2019.05.02.01).

Version history

  1. Received: July 26, 2021
  2. Preprint posted: August 28, 2021 (view preprint)
  3. Accepted: February 3, 2022
  4. Accepted Manuscript published: February 9, 2022 (version 1)
  5. Version of Record published: February 24, 2022 (version 2)

Copyright

© 2022, Cortenbach et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kimberley RG Cortenbach
  2. Alexander HJ Staal
  3. Teske Schoffelen
  4. Mark AJ Gorris
  5. Lieke L Van der Woude
  6. Anne FM Jansen
  7. Paul Poyck
  8. Robert Jan Van Suylen
  9. Peter C Wever
  10. Chantal P Bleeker-Rovers
  11. Mangala Srinivas
  12. Konnie M Hebeda
  13. Marcel van Deuren
  14. Jos W Van der Meer
  15. Jolanda M De Vries
  16. Roland RJ Van Kimmenade
(2022)
Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry
eLife 11:e72486.
https://doi.org/10.7554/eLife.72486

Share this article

https://doi.org/10.7554/eLife.72486

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