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Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature upon SARS-CoV-2 sensing by monocytes in COVID-19

Allison K. Maher, Katie L. Burnham, Emma Jones, Laury Baillon, Claudia Selck, Nicolas Giang, View ORCID ProfileRafael Argüello, Charlotte-Eve Short, Rachael Quinlan, Wendy S. Barclay, Nichola Cooper, Graham P. Taylor, Emma E. Davenport, View ORCID ProfileMargarita Dominguez-Villar
doi: https://doi.org/10.1101/2022.04.03.486830
Allison K. Maher
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Katie L. Burnham
2Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
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Emma Jones
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Laury Baillon
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Claudia Selck
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Nicolas Giang
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Rafael Argüello
3Aix Marseille Université, CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy, Marseille, France
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  • ORCID record for Rafael Argüello
Charlotte-Eve Short
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Rachael Quinlan
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Wendy S. Barclay
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Nichola Cooper
4Department of Immunology and Inflammation, Faculty of Medicine, Imperial College London, UK
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Graham P. Taylor
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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Emma E. Davenport
2Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
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Margarita Dominguez-Villar
1Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
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  • ORCID record for Margarita Dominguez-Villar
  • For correspondence: m.dominguez-villar@imperial.ac.uk
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Abstract

Alterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+ monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found that ex vivo isolated CD14+ monocytes from mild and moderate COVID-19 patients display specific patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as altered expression of histone marks and a dysfunctional metabolic profile. Decreased NFκB activation in COVID-19 monocytes ex vivo is accompanied by an intact type I IFN antiviral response. Subsequent pathogen sensing ex vivo led to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NFκB-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes. Transcriptionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by increased expression of pathways involved in hemostasis and immunothrombosis. In response to SARS-CoV-2 or other viral or bacterial components, monocytes displayed defects in the epigenetic remodelling and metabolic reprogramming that usually occurs upon pathogen sensing in innate immune cells. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 03, 2022.
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Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature upon SARS-CoV-2 sensing by monocytes in COVID-19
Allison K. Maher, Katie L. Burnham, Emma Jones, Laury Baillon, Claudia Selck, Nicolas Giang, Rafael Argüello, Charlotte-Eve Short, Rachael Quinlan, Wendy S. Barclay, Nichola Cooper, Graham P. Taylor, Emma E. Davenport, Margarita Dominguez-Villar
bioRxiv 2022.04.03.486830; doi: https://doi.org/10.1101/2022.04.03.486830
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Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature upon SARS-CoV-2 sensing by monocytes in COVID-19
Allison K. Maher, Katie L. Burnham, Emma Jones, Laury Baillon, Claudia Selck, Nicolas Giang, Rafael Argüello, Charlotte-Eve Short, Rachael Quinlan, Wendy S. Barclay, Nichola Cooper, Graham P. Taylor, Emma E. Davenport, Margarita Dominguez-Villar
bioRxiv 2022.04.03.486830; doi: https://doi.org/10.1101/2022.04.03.486830

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