Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/72486 |
| _version_ | 1811227403030102016 |
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| author | Kimberley RG Cortenbach Alexander HJ Staal Teske Schoffelen Mark AJ Gorris Lieke L Van der Woude Anne FM Jansen Paul Poyck Robert Jan Van Suylen Peter C Wever Chantal P Bleeker-Rovers Mangala Srinivas Konnie M Hebeda Marcel van Deuren Jos W Van der Meer Jolanda M De Vries Roland RJ Van Kimmenade |
| author_facet | Kimberley RG Cortenbach Alexander HJ Staal Teske Schoffelen Mark AJ Gorris Lieke L Van der Woude Anne FM Jansen Paul Poyck Robert Jan Van Suylen Peter C Wever Chantal P Bleeker-Rovers Mangala Srinivas Konnie M Hebeda Marcel van Deuren Jos W Van der Meer Jolanda M De Vries Roland RJ Van Kimmenade |
| author_sort | Kimberley RG Cortenbach |
| collection | DOAJ |
| description | 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 systems.
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. Finally, Q fever AAAs did not contain any well-defined granulomas.
Conclusions: These findings demonstrate that despite the presence of pro-inflammatory effector cells, persistent local infection with C. burnetii is associated with an immune-suppressed microenvironment.
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]. |
| first_indexed | 2024-04-12T09:40:46Z |
| format | Article |
| id | doaj.art-1e24405511e940f389f690a5a298a7af |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:40:46Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1e24405511e940f389f690a5a298a7af2022-12-22T03:38:04ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.72486Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistryKimberley RG Cortenbach0https://orcid.org/0000-0002-2717-5527Alexander HJ Staal1Teske Schoffelen2Mark AJ Gorris3Lieke L Van der Woude4Anne FM Jansen5Paul Poyck6Robert Jan Van Suylen7Peter C Wever8Chantal P Bleeker-Rovers9Mangala Srinivas10Konnie M Hebeda11https://orcid.org/0000-0002-4181-3302Marcel van Deuren12Jos W Van der Meer13Jolanda M De Vries14Roland RJ Van Kimmenade15https://orcid.org/0000-0002-8207-8906Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Surgery, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Pathology, Jeroen Bosch Ziekenhuis, 's Hertogenbosch, NetherlandsDepartment of Medical Microbiology and Infection Control, Jeroen Bosch Ziekenhuis, 's Hertogenbosch, NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands; Department of Cell Biology and Immunology, Wageningen University, Wageningen, NetherlandsDepartment of Pathology, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Cardiology, Radboud University Medical Centre, Nijmegen, NetherlandsBackground: 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 systems. 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. Finally, Q fever AAAs did not contain any well-defined granulomas. Conclusions: These findings demonstrate that despite the presence of pro-inflammatory effector cells, persistent local infection with C. burnetii is associated with an immune-suppressed microenvironment. 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].https://elifesciences.org/articles/72486aortic aneurysminflammationQ fevermultiplex immunohistochemistry |
| spellingShingle | Kimberley RG Cortenbach Alexander HJ Staal Teske Schoffelen Mark AJ Gorris Lieke L Van der Woude Anne FM Jansen Paul Poyck Robert Jan Van Suylen Peter C Wever Chantal P Bleeker-Rovers Mangala Srinivas Konnie M Hebeda Marcel van Deuren Jos W Van der Meer Jolanda M De Vries Roland RJ Van Kimmenade Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry eLife aortic aneurysm inflammation Q fever multiplex immunohistochemistry |
| title | Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry |
| title_full | Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry |
| title_fullStr | Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry |
| title_full_unstemmed | Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry |
| title_short | Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry |
| title_sort | differences in local immune cell landscape between q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry |
| topic | aortic aneurysm inflammation Q fever multiplex immunohistochemistry |
| url | https://elifesciences.org/articles/72486 |
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