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

Autor:	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., Hetherington C; Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom., Boardman SA; Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom., Clark JJ; Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom., Sharma P; Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom., Subramaniam K; Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom., Tharmaratnam K; Department of Health Data Science, Institute of Population Health, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom., Needham EJ; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom., Williams R; Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom., Huang Y; Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom., Wood GK; Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom., Collie C; Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom., Fower A; Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom., Fox H; Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom., Ellul MA; Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom., Held M; Centre for Cell Imaging, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom., Egbe FN; Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom., Griffiths M; Clinical Infection Microbiology and Immunology, Institute of Infection Ecology and Veterinary Sciences, University of Liverpool, Liverpool, United Kingdom., 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., 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., 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., Cavanagh J; College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom., Irani SR; Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom., Vincent A; Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom., Stewart JP; Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom., 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., Menon DK; Division of Anaesthesia, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, United Kingdom., 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.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Oct 14; Vol. 15, pp. 1440324. Date of Electronic Publication: 2024 Oct 14 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1440324
Abstrakt:	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. Competing Interests: 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. (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.)
Databáze:	MEDLINE
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