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

Kimberley Rg Cortenbach,Alexander Hj Staal,Robert Jan Van Suylen,Marcel Van Deuren,Jos W Van Der Meer,Jolanda M De Vries,Roland Rj Van Kimmenade,Anne Fm Jansen,Peter C Wever,Teske Schoffelen,Paul Poyck,Chantal P Bleeker-Rovers,Mangala Srinivas,Mark Aj Gorris,Konnie M Hebeda,Lieke L Van Der Woude

doi:10.7554/elife.72486

Abstract

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. 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. 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. 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. 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].

Highlights

Q fever is a zoonosis caused by the Gram-negative intracellular bacterium Coxiella burnetii (C.burnetii), with natural reservoirs in a wide range of wild and domestic animals
Immune cell activation in Q fever, atherosclerotic, and acutely infected abdominal aortic aneurysm (AAA) compared to normal aortas
When correcting numbers of T cell subsets for infiltrate area, we found an increase in the number of CD3+CD8+ cytotoxic T cells in Q fever AAA compared to atherosclerotic AAA

Summary

Introduction

Q fever is a zoonosis caused by the Gram-negative intracellular bacterium Coxiella burnetii (C.burnetii), with natural reservoirs in a wide range of wild and domestic animals. [3] Chronic Q fever manifests as endocarditis or vascular Q fever, i.e., infection of an abdominal aortic aneurysm (AAA). Vascular manifestations of Q fever can have severe clinical consequences. In a population of proven and probable vascular manifestations of Q fever patients according to the Dutch consensus guideline, a Dutch cohort study has described that complications had occurred in 61% of the cases. 25% of patients had a definitely or probably chronic Q fever related cause of death. [6] In addition, serological screening of patients with aorto-iliac disease, e.g., aneurysms or previous vascular reconstructions, demonstrated that 16.9% was seropositive for Q fever, of which 30.8% suffered from chronic Q fever. Chronic Q fever is a zoonosis caused by the bacterium Coxiella burnetii which can manifest as infection of an abdominal aortic aneurysm (AAA). Whereas previous studies have focused on inflammatory processes in blood, the aim of this study was to investigate local inflammation in aortic tissue

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