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Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs.
Weeratunga, Praveen; Denney, Laura; Bull, Joshua A; Repapi, Emmanouela; Sergeant, Martin; Etherington, Rachel; Vuppussetty, Chaitanya; Turner, Gareth D H; Clelland, Colin; Woo, Jeongmin; Cross, Amy; Issa, Fadi; de Andrea, Carlos Eduardo; Melero Bermejo, Ignacio; Sims, David; McGowan, Simon; Zurke, Yasemin-Xiomara; Ahern, David J; Gamez, Eddie C; Whalley, Justin; Richards, Duncan; Klenerman, Paul; Monaco, Claudia; Udalova, Irina A; Dong, Tao; Antanaviciute, Agne; Ogg, Graham; Knight, Julian C; Byrne, Helen M; Taylor, Stephen; Ho, Ling-Pei.
Affiliation
  • Weeratunga P; MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Denney L; MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Bull JA; Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, UK.
  • Repapi E; MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Sergeant M; MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Etherington R; MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Vuppussetty C; MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Turner GDH; Department of Cellular Pathology and Radcliffe Department of Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Clelland C; Anatomic Pathology, Weill Cornell Medical College, Doha, Qatar.
  • Woo J; MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Cross A; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • Issa F; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • de Andrea CE; Navarra Institute for Health Research, Pamplona, Spain.
  • Melero Bermejo I; Navarra Institute for Health Research, Pamplona, Spain.
  • Sims D; MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • McGowan S; MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Zurke YX; Kennedy Institute for Rheumatology, University of Oxford, Oxford, UK.
  • Ahern DJ; Kennedy Institute for Rheumatology, University of Oxford, Oxford, UK.
  • Gamez EC; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Whalley J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Richards D; Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Diseases, University of Oxford, Oxford, UK.
  • Klenerman P; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Monaco C; Kennedy Institute for Rheumatology, University of Oxford, Oxford, UK.
  • Udalova IA; Kennedy Institute for Rheumatology, University of Oxford, Oxford, UK.
  • Dong T; MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Antanaviciute A; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Ogg G; MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Knight JC; MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Byrne HM; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
  • Taylor S; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Ho LP; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
Nat Commun ; 14(1): 7216, 2023 11 08.
Article in En | MEDLINE | ID: mdl-37940670
ABSTRACT
Single cell spatial interrogation of the immune-structural interactions in COVID -19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we develop a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method reveals a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium. Of note, a highly active cluster of immature neutrophils and CD8 T cells, is found spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings offer further insights into how immune cells interact in the lungs of severe COVID-19 disease. We provide our pipeline [Spatial Omics Oxford Pipeline (SpOOx)] and visual-analytical tool, Multi-Dimensional Viewer (MDV) software, as a resource for spatial analysis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: COVID-19 / Neutrophils Limits: Humans Language: En Journal: Nat Commun Year: 2023 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: COVID-19 / Neutrophils Limits: Humans Language: En Journal: Nat Commun Year: 2023 Document type: Article