Rapid Inflammasome Activation Is Attenuated in Post-Myocardial Infarction Monocytes
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Rapid Inflammasome Activation Is Attenuated in Post-Myocardial Infarction Monocytes. / Giral, Hector; Franke, Vedran; Moobed, Minoo; Müller, Maja F; Lübking, Laura; James, Divya Maria; Hartung, Johannes; Kuschnerus, Kira; Meteva, Denitsa; Seppelt, Claudio; Jakob, Philipp; Klingenberg, Roland; Kränkel, Nicolle; Leistner, David; Zeller, Tanja; Blankenberg, Stefan; Zimmermann, Friederike; Haghikia, Arash; Lüscher, Thomas F; Akalin, Altuna; Landmesser, Ulf; Kratzer, Adelheid.
In: FRONT IMMUNOL, Vol. 13, 857455, 2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Rapid Inflammasome Activation Is Attenuated in Post-Myocardial Infarction Monocytes
AU - Giral, Hector
AU - Franke, Vedran
AU - Moobed, Minoo
AU - Müller, Maja F
AU - Lübking, Laura
AU - James, Divya Maria
AU - Hartung, Johannes
AU - Kuschnerus, Kira
AU - Meteva, Denitsa
AU - Seppelt, Claudio
AU - Jakob, Philipp
AU - Klingenberg, Roland
AU - Kränkel, Nicolle
AU - Leistner, David
AU - Zeller, Tanja
AU - Blankenberg, Stefan
AU - Zimmermann, Friederike
AU - Haghikia, Arash
AU - Lüscher, Thomas F
AU - Akalin, Altuna
AU - Landmesser, Ulf
AU - Kratzer, Adelheid
N1 - Copyright © 2022 Giral, Franke, Moobed, Müller, Lübking, James, Hartung, Kuschnerus, Meteva, Seppelt, Jakob, Klingenberg, Kränkel, Leistner, Zeller, Blankenberg, Zimmermann, Haghikia, Lüscher, Akalin, Landmesser and Kratzer.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Humans
KW - Inflammasomes/metabolism
KW - Interleukin-18/metabolism
KW - Interleukin-1beta/metabolism
KW - Monocytes
KW - Myocardial Infarction/pathology
KW - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
KW - Percutaneous Coronary Intervention
U2 - 10.3389/fimmu.2022.857455
DO - 10.3389/fimmu.2022.857455
M3 - SCORING: Journal article
C2 - 35558073
VL - 13
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
M1 - 857455
ER -
