Frontiers in Immunology (Apr 2022)
Rapid Inflammasome Activation Is Attenuated in Post-Myocardial Infarction Monocytes
- Hector Giral,
- Hector Giral,
- Vedran Franke,
- Minoo Moobed,
- Maja F. Müller,
- Laura Lübking,
- Divya Maria James,
- Johannes Hartung,
- Kira Kuschnerus,
- Kira Kuschnerus,
- Denitsa Meteva,
- Denitsa Meteva,
- Claudio Seppelt,
- Claudio Seppelt,
- Philipp Jakob,
- Philipp Jakob,
- Philipp Jakob,
- Philipp Jakob,
- Roland Klingenberg,
- Nicolle Kränkel,
- Nicolle Kränkel,
- David Leistner,
- David Leistner,
- David Leistner,
- Tanja Zeller,
- Tanja Zeller,
- Stefan Blankenberg,
- Stefan Blankenberg,
- Friederike Zimmermann,
- Friederike Zimmermann,
- Arash Haghikia,
- Arash Haghikia,
- Thomas F. Lüscher,
- Altuna Akalin,
- Ulf Landmesser,
- Ulf Landmesser,
- Ulf Landmesser,
- Adelheid Kratzer,
- Adelheid Kratzer
Affiliations
- Hector Giral
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Hector Giral
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Vedran Franke
- Max Delbrück Center, The Berlin Institute for Medical Systems Biology, Berlin, Germany
- Minoo Moobed
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Maja F. Müller
- Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
- Laura Lübking
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Divya Maria James
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Johannes Hartung
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Kira Kuschnerus
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Kira Kuschnerus
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Denitsa Meteva
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Denitsa Meteva
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Claudio Seppelt
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Claudio Seppelt
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Philipp Jakob
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Philipp Jakob
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Philipp Jakob
- Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
- Philipp Jakob
- Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
- Roland Klingenberg
- Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
- Nicolle Kränkel
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Nicolle Kränkel
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- David Leistner
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- David Leistner
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- David Leistner
- Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
- Tanja Zeller
- Department of Cardiology, University Heart and Vascular Center, Hamburg, Germany
- Tanja Zeller
- DZHK (German Center for Cardiovascular Research), Partner Site Hamburg, Lübeck, Kiel, Hamburg, Germany
- Stefan Blankenberg
- Department of Cardiology, University Heart and Vascular Center, Hamburg, Germany
- Stefan Blankenberg
- DZHK (German Center for Cardiovascular Research), Partner Site Hamburg, Lübeck, Kiel, Hamburg, Germany
- Friederike Zimmermann
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Friederike Zimmermann
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Arash Haghikia
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Arash Haghikia
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Thomas F. Lüscher
- Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland
- Altuna Akalin
- Max Delbrück Center, The Berlin Institute for Medical Systems Biology, Berlin, Germany
- Ulf Landmesser
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Ulf Landmesser
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Ulf Landmesser
- Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
- Adelheid Kratzer
- Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Adelheid Kratzer
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- DOI
- https://doi.org/10.3389/fimmu.2022.857455
- Journal volume & issue
-
Vol. 13
Abstract
Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release. Both classical and intermediate monocytes from healthy donors exhibited robust CASP1 activation, but only classical monocytes produced high mature interleukin-18 (IL18) release. We also recruited a limited number of coronary artery disease (CAD, n=31) and AMI (n=29) patients to evaluate their inflammasome function and expression profiles. Surprisingly, monocyte subpopulations isolated from blood collected during percutaneous coronary intervention (PCI) from AMI patients presented diminished CASP1 activity and abrogated IL18 release despite increased NLRP3 gene expression. This unexpected attenuated rapid inflammasome activation was accompanied by a significant increase of TNFAIP3 and IRAKM expression. Moreover, TNFAIP3 protein levels of circulating monocytes showed positive correlation with high sensitive troponin T (hsTnT), implying an association between TNFAIP3 upregulation and the severity of tissue injury. We suggest this monocyte attenuation to be a protective phenotype aftermath following a very early inflammatory wave in the ischemic area. Damage-associated molecular patterns (DAMPs) or other signals trigger a transitory negative feedback loop within newly recruited circulating monocytes as a mechanism to reduce post-injury tissue damage.
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