Frontiers in Immunology (Oct 2024)
Pulmonary SARS-CoV-2 infection leads to para-infectious immune activation in the brain
- Cordelia Dunai,
- Cordelia Dunai,
- Claire Hetherington,
- Sarah A. Boardman,
- Jordan J. Clark,
- Parul Sharma,
- Krishanthi Subramaniam,
- Kukatharmini Tharmaratnam,
- Edward J. Needham,
- Robyn Williams,
- Yun Huang,
- Greta K. Wood,
- Ceryce Collie,
- Andrew Fower,
- Hannah Fox,
- Mark A. Ellul,
- Marie Held,
- Franklyn N. Egbe,
- Michael Griffiths,
- Tom Solomon,
- Tom Solomon,
- Tom Solomon,
- Gerome Breen,
- Gerome Breen,
- Anja Kipar,
- Anja Kipar,
- Jonathan Cavanagh,
- Sarosh R. Irani,
- Angela Vincent,
- James P. Stewart,
- Leonie S. Taams,
- David K. Menon,
- Benedict D. Michael,
- Benedict D. Michael,
- Benedict D. Michael
Affiliations
- Cordelia Dunai
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom
- Cordelia Dunai
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Claire Hetherington
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Sarah A. Boardman
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Jordan J. Clark
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Parul Sharma
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Krishanthi Subramaniam
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Kukatharmini Tharmaratnam
- Department of Health Data Science, Institute of Population Health, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
- Edward J. Needham
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
- Robyn Williams
- Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
- Yun Huang
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Greta K. Wood
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Ceryce Collie
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Andrew Fower
- Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
- Hannah Fox
- Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
- Mark A. Ellul
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Marie Held
- Centre for Cell Imaging, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom
- Franklyn N. Egbe
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Michael Griffiths
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Tom Solomon
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom
- Tom Solomon
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Tom Solomon
- Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
- Gerome Breen
- Department of Social, Genetic & Developmental Psychiatry Centre, School of Mental Health & Psychological Sciences, King’s College London, London, United Kingdom
- Gerome Breen
- 0NIHR Maudsley Biomedical Research Centre, King’s College London, London, United Kingdom
- Anja Kipar
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Anja Kipar
- 1Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
- Jonathan Cavanagh
- 2College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
- Sarosh R. Irani
- Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
- Angela Vincent
- Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
- James P. Stewart
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
- Leonie S. Taams
- 3Centre 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
- 4Division of Anaesthesia, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, United Kingdom
- Benedict D. Michael
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom
- Benedict D. Michael
- Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom
- Benedict D. Michael
- Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
- DOI
- https://doi.org/10.3389/fimmu.2024.1440324
- Journal volume & issue
-
Vol. 15
Abstract
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 in vitro experiments demonstrated that the filtered supernatant from SARS-CoV-2 virion exposed brain endothelial cells induced activation of uninfected microglia. This model successfully recreates SARS-CoV-2 virus-associated para-infectious brain inflammation which can be used to study the pathophysiology of the neurological complications and the identification of potential immune targets for treatment.
Keywords
