AIM2 levels and DNA-triggered inflammasome response are increased in peripheral leukocytes of patients with abdominal aortic aneurysm
Objective and design
Abdominal aortic aneurysm (AAA) is heavily infiltrated with leukocytes, expressing the DNA sensor absent in melanoma 2 (AIM2) and other inflammasome components.
Using multicolour flow cytometry, we here compared the expression of the inflammasome components AIM2, NLRP3, and ASC in different peripheral immune cells derived from AAA patients with those from non-AAA patients in a case–control study. In parallel, peripheral blood mononuclear cells (PBMC) of AAA patients and controls were stimulated in vitro with poly-dA:dT or lipopolysaccharide (LPS) to analyze inflammasome activation.
AIM2 expression was significantly increased in peripheral granulocytes (P = 0.026), monocytes (P = 0.007), B lymphocytes (P < 0.0001), and T lymphocytes (P = 0.004) of AAA patients. Expression of other inflammasome components did not differ between the groups. Following in vitro stimulation with foreign DNA, PBMC derived from AAA patients released significantly more IL-1β (P = 0.022) into the supernatant than PBMC from control patients. In contrast, IL-1β release upon LPS stimulation did not differ between the PBMC groups.
The data indicate the increased activation of an AIM2 inflammasome in peripheral immune cells of AAA patients and point to a systemic AIM2-associated immune response to AAA.
KeywordsInflammasome Innate immunity Abdominal aortic aneurysm FACS Flow cytometry PBMC
We thank Anja Spieler (Department of Vascular and Endovascular Surgery of the University Hospital Heidelberg, Germany) for excellent technical assistance.
We acknowledge financial support by the Department of Vascular and Endovascular surgery of the University Hospital Heidelberg, Germany. This research was supported in part by a grant of the Deutsche Forschungsgemeinschaft (DFG; No. 323488362) to MW and SD.
Compliance with ethical standards
Conflict of interest
Xianghui Xiao has received financial support from the German Society of Vascular Surgery and Vascular Medicine for attending the annual meeting of the society in 2017. Maani Hakimi is CEO of CODE Medical Frankfurt GbR, Germany. Dittmar Böckler is consultant for Medtronic, W.L Gore & Ass. Endologix. The authors have no competing interests. MW, GW, YS, and SD have no conflict of interest for this publication.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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