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Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection.
Long, Merete B; Howden, Andrew J M; Keir, Holly R; Rollings, Christina M; Giam, Yan Hui; Pembridge, Thomas; Delgado, Lilia; Abo-Leyah, Hani; Lloyd, Amy F; Sollberger, Gabriel; Hull, Rebecca; Gilmour, Amy; Hughes, Chloe; New, Benjamin J M; Cassidy, Diane; Shoemark, Amelia; Richardson, Hollian; Lamond, Angus I; Cantrell, Doreen A; Chalmers, James D; Brenes, Alejandro J.
Afiliación
  • Long MB; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Howden AJM; Indicates equal contribution.
  • Keir HR; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.
  • Rollings CM; Indicates equal contribution.
  • Giam YH; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Pembridge T; Indicates equal contribution.
  • Delgado L; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.
  • Abo-Leyah H; Indicates equal contribution.
  • Lloyd AF; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Sollberger G; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Hull R; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Gilmour A; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Hughes C; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.
  • New BJM; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.
  • Cassidy D; Max Planck Institute for Infection Biology, Berlin, Germany.
  • Shoemark A; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
  • Richardson H; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Lamond AI; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Cantrell DA; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
  • Chalmers JD; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
  • Brenes AJ; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Eur Respir J ; 63(3)2024 Mar.
Article en En | MEDLINE | ID: mdl-38097207
ABSTRACT

BACKGROUND:

Neutrophils are important in the pathophysiology of coronavirus disease 2019 (COVID-19), but the molecular changes contributing to altered neutrophil phenotypes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We used quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes immediately following acute SARS-CoV-2 infection and during recovery.

METHODS:

Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May to December 2020). Patients were enrolled within 96 h of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID-19 acute lower respiratory tract infection (LRTI) and age-matched noninfected controls. Neutrophils were isolated from peripheral blood and analysed using mass spectrometry. COVID-19 severity and recovery were defined using the World Health Organization ordinal scale.

RESULTS:

Neutrophil proteomes from 84 COVID-19 patients were compared to those from 91 LRTI and 42 control participants. 5800 neutrophil proteins were identified, with >1700 proteins significantly changed in neutrophils from COVID-19 patients compared to noninfected controls. Neutrophils from COVID-19 patients initially all demonstrated a strong interferon signature, but this signature rapidly declined in patients with severe disease. Severe disease was associated with increased abundance of proteins involved in metabolism, immunosuppression and pattern recognition, while delayed recovery from COVID-19 was associated with decreased granule components and reduced abundance of metabolic proteins, chemokine and leukotriene receptors, integrins and inhibitory receptors.

CONCLUSIONS:

SARS-CoV-2 infection results in the sustained presence of circulating neutrophils with distinct proteomes suggesting altered metabolic and immunosuppressive profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: COVID-19 Límite: Humans Idioma: En Revista: Eur Respir J Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: COVID-19 Límite: Humans Idioma: En Revista: Eur Respir J Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido