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

Lookup NU author(s): Dr Catherine Park, Dr Suzanne Cormack, Dr Ashfaq Mohammed, Dr Stephen Boag, Dr Karim Bennaceur, Dr Kateryna Sopova, Dr Gavin RichardsonORCiD, Professor Konstantinos StellosORCiD, Professor Ioakim SpyridopoulosORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Aims: Latent 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 Results: We 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.Conclusion: We 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.

Publication metadata

Author(s): Spray L, Park C, Cormack S, Mohammed A, Panahi P, Boag S, Bennaceur K, Sopova K, Richardson G, Stangl V, Rech L, Rainer P, Ramos G, Hofmann U, Stellos K, Spyridopoulos I

Publication type: Article

Publication status: Published

Journal: Frontiers in Immunology

Year: 2021

Volume: 12

Online publication date: 05/05/2021

Acceptance date: 20/04/2021

Date deposited: 12/05/2021

ISSN (electronic): 1664-3224

Publisher: Frontiers Media SA


DOI: 10.3389/fimmu.2021.605857


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Funder referenceFunder name
I 4168-B
National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre
PG/18/25/33587British Heart Foundation
the Austrian Science Fund
the Interdisciplinary Center for Clinical Research W├╝rzburg