The Fractalkine Receptor CX3CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling

AimsLatent cytomegalovirus (CMV) infection is associated with adverse cardiovascular outcomes. Virus-specific CX3CR1+ effector memory T-cells may be instrumental in this process due to their pro-inflammatory properties. We investigated the role of CX3CR1 (fractalkine receptor) in CMV-related lymphoc...

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Bibliographic Details
Published in:Frontiers in immunology 2021-05, Vol.12, p.605857-605857
Main Authors: Spray, Luke, Park, Catherine, Cormack, Suzanne, Mohammed, Ashfaq, Panahi, Pedram, Boag, Stephen, Bennaceur, Karim, Sopova, Kateryna, Richardson, Gavin, Stangl, Verena M., Rech, Lavinia, Rainer, Peter P., Ramos, Gustavo Campos, Hofmann, Ulrich, Stellos, Konstantinos, Spyridopoulos, Ioakim
Format: Article
Language:English
Subjects:
acute myocardial infarction
cardiac MRI
CX3CR1
cytomegalovirus
Immunology
remodeling
T-lymphocytes
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Summary:AimsLatent cytomegalovirus (CMV) infection is associated with adverse cardiovascular outcomes. Virus-specific CX3CR1+ effector memory T-cells may be instrumental in this process due to their pro-inflammatory properties. We investigated the role of CX3CR1 (fractalkine receptor) in CMV-related lymphocyte kinetics and cardiac remodeling in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).Methods and ResultsWe retrospectively analysed lymphocyte count, troponin, and survival in 4874 STEMI/pPCI patients, evaluated lymphocyte kinetics during reperfusion in a prospective cohort, and obtained sequential cardiac MRI (cMRI) to assess remodeling. Pre-reperfusion lymphopenia independently predicted mortality at 7.5 years. Prior to reperfusion, CCR7+ T-lymphocytes appeared to be depleted. After reperfusion, T-lymphocytes expressing CX3CR1 were depleted predominantly in CMV-seropositive patients. During ischaemia/reperfusion, a drop in CX3CR1+ T-lymphocytes was significantly linked with microvascular obstruction in CMV+ patients, suggesting increased fractalkine-receptor interaction. At 12 weeks, CMV+ patients displayed adverse LV remodeling.ConclusionWe show that lymphopenia occurs before and after reperfusion in STEMI by different mechanisms and predicts long-term outcome. In CMV+ patients, increased fractalkine induction and sequestration of CX3CR1+ T-cells may contribute to adverse remodeling, suggesting a pro-inflammatory pathomechanism which presents a novel therapeutic target.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.605857