TY - JOUR AU - Spray, Luke AU - Park, Catherine AU - Cormack, Suzanne AU - Mohammed, Ashfaq AU - Panahi, Pedram AU - Boag, Stephen AU - Bennaceur, Karim AU - Sopova, Kateryna AU - Richardson, Gavin AU - Stangl, Verena M. AU - Rech, Lavinia AU - Rainer, Peter P. AU - Ramos, Gustavo Campos AU - Hofmann, Ulrich AU - Stellos, Konstantinos AU - Spyridopoulos, Ioakim PY - 2021 M3 - Original Research TI - The Fractalkine Receptor CX3CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling JO - Frontiers in Immunology UR - https://www.frontiersin.org/articles/10.3389/fimmu.2021.605857 VL - 12 SN - 1664-3224 N2 - 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. ER -