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Journal article
Mapping CMV-related immune signatures in blood, aorta and perivascular mediastinal adipose tissue
Philosophical Transactions B, Vol.380(1938), 20240401
2025
PMID: 41194668
Abstract
Cytomegalovirus (CMV) establishes lifelong latency and is linked to immunosenescence in older and immunocompromised individuals. We hypothesize that CMV drives systemic and tissue-specific immune changes that may contribute to cardiovascular disease (CVD). Thoracic aorta, blood and perivascular mediastinal adipose tissue from cardiac surgery patients (n = 11) were processed within 30–60 min of excision. CMV IgG titres were quantified through ELISA to determine CMV status: CMV(−) (n = 4) and CMV(+) (n = 7). Immune profiling was performed using flow cytometry and single-cell RNA sequencing. Analyses included MiloR and differential gene expression. Participants (mean age 69.7 ± 8.4 years) were 80% male and 70% Caucasian. CMV(−) and CMV(+) participants had mean IgG titres of 0.038 and 13.55 IU ml−1, respectively. CD8+ T-cells expressing CD57+, GPR56+ and CX3CR1+ (CGC) were increased in the blood of CMV(+) participants. In the aorta of CMV(+) participants, CD8+ T cells and CD4+ T cells had decreased HLA-C expression and suppressed interferon-α pathways. In contrast, the TNF-α signalling pathway was increased. CMV infection shapes immune responses and in this pilot, we observed suppression of interferon-α signalling and increased TNF-α-associated pathways in the aorta. Larger studies are needed to define how CMV-driven immune remodelling contributes to CVD.
This article is part of the discussion meeting issue ‘The indirect effects of cytomegalovirus infection: mechanisms and consequences.’
Details
- Title
- Mapping CMV-related immune signatures in blood, aorta and perivascular mediastinal adipose tissue
- Authors/Creators
- Cassia Labeb - Vanderbilt University Medical CenterLaventa M. Obare - Vanderbilt University Medical CenterQuanhu Sheng - Vanderbilt UniversityXiuqi Zhang - Vanderbilt University Medical CenterRama Gangula - Vanderbilt University Medical CenterKisyua Nthenge - Vanderbilt University Medical CenterSamuel S. Bailin - Vanderbilt University Medical CenterMona Mashayekhi - Vanderbilt University Medical CenterVictoria R. Stephens - Vanderbilt University Medical CenterLindsey Stolze - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37232, USAStephen Priest - Vanderbilt University Medical CenterJordan C. Malone - Vanderbilt University Medical CenterJared M. Oakes - Vanderbilt University Medical CenterCurtis L. Gabriel - Vanderbilt University Medical CenterElizabeth J. PhillipsSpyros A. Kalams - Vanderbilt University Medical CenterSimon A. MallalSara Gianella - University of California San DiegoJohn R. Koethe - Vanderbilt University Medical CenterYan Ru Su - Vanderbilt University Medical CenterTarek Absi - Vanderbilt University Medical CenterCelestine N. Wanjalla - Vanderbilt University Medical Center
- Publication Details
- Philosophical Transactions B, Vol.380(1938), 20240401
- Publisher
- The Royal Society
- Number of pages
- 13
- Grant note
- 2021193 / Doris Duke Charitable Foundation (http://dx.doi.org/10.13039/100000862) National Institute of Allergy and Infectious Diseases (http://dx.doi.org/10.13039/100000060) National Center for Advancing Translational Sciences (http://dx.doi.org/10.13039/100006108) K23HL156759-01A1 / National Heart, Lung and Blood Institute (NHLBI) 1021480 / Burroughs Wellcome Fund (http://dx.doi.org/10.13039/100000861)
- Identifiers
- 991005830350107891
- Copyright
- © 2025 The Authors.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.161 Virology - Identification & Sequencing
- 1.161.711 Cytomegalovirus Infections
- Web Of Science research areas
- Biology
- ESI research areas
- Biology & Biochemistry