Pulmonary SARS-CoV-2 infection leads to para-infectious immune activation in the brain.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2024
Historique:
received: 29 05 2024
accepted: 04 09 2024
medline: 30 10 2024
pubmed: 30 10 2024
entrez: 30 10 2024
Statut: epublish

Résumé

Neurological complications, including encephalopathy and stroke, occur in a significant proportion of COVID-19 cases but viral protein is seldom detected in the brain parenchyma. To model this situation, we developed a novel low-inoculum K18-hACE2 mouse model of SARS-CoV-2 infection during which active viral replication was consistently seen in mouse lungs but not in the brain. We found that several mediators previously associated with encephalopathy in clinical samples were upregulated in the lung, including CCL2, and IL-6. In addition, several inflammatory mediations, including CCL4, IFNγ, IL-17A, were upregulated in the brain, associated with microglial reactivity. Parallel

Identifiants

pubmed: 39474424
doi: 10.3389/fimmu.2024.1440324
pmc: PMC11519853
doi:

Substances chimiques

Angiotensin-Converting Enzyme 2 EC 3.4.17.23
Cytokines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1440324

Informations de copyright

Copyright © 2024 Dunai, Hetherington, Boardman, Clark, Sharma, Subramaniam, Tharmaratnam, Needham, Williams, Huang, Wood, Collie, Fower, Fox, Ellul, Held, Egbe, Griffiths, Solomon, Breen, Kipar, Cavanagh, Irani, Vincent, Stewart, Taams, Menon and Michael.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Cordelia Dunai (C)

NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom.
Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Claire Hetherington (C)

Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Sarah A Boardman (SA)

Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Jordan J Clark (JJ)

Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.

Parul Sharma (P)

Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.

Krishanthi Subramaniam (K)

Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.

Kukatharmini Tharmaratnam (K)

Department of Health Data Science, Institute of Population Health, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.

Edward J Needham (EJ)

Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Robyn Williams (R)

Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.

Yun Huang (Y)

Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Greta K Wood (GK)

Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Ceryce Collie (C)

Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Andrew Fower (A)

Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.

Hannah Fox (H)

Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.

Mark A Ellul (MA)

Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Marie Held (M)

Centre for Cell Imaging, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.

Franklyn N Egbe (FN)

Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Michael Griffiths (M)

Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.

Tom Solomon (T)

NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom.
Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.
Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.

Gerome Breen (G)

Department of Social, Genetic & Developmental Psychiatry Centre, School of Mental Health & Psychological Sciences, King's College London, London, United Kingdom.
NIHR Maudsley Biomedical Research Centre, King's College London, London, United Kingdom.

Anja Kipar (A)

Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

Jonathan Cavanagh (J)

College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Sarosh R Irani (SR)

Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.

Angela Vincent (A)

Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.

James P Stewart (JP)

Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.

Leonie S Taams (LS)

Centre for Inflammation Biology and Cancer Immunology, Department of Inflammation Biology, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.

David K Menon (DK)

Division of Anaesthesia, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, United Kingdom.

Benedict D Michael (BD)

NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom.
Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom.
Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.

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