Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry
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.
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Vascular Q fever inflammationDryad Digital Repository, doi:10.5061/dryad.bzkh189b4.
Article and author information
Author details
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
- 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
- Received: July 26, 2021
- Preprint posted: August 28, 2021 (view preprint)
- Accepted: February 3, 2022
- Accepted Manuscript published: February 9, 2022 (version 1)
- 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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