Nature Communications (Nov 2023)
Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs
- Praveen Weeratunga,
- Laura Denney,
- Joshua A. Bull,
- Emmanouela Repapi,
- Martin Sergeant,
- Rachel Etherington,
- Chaitanya Vuppussetty,
- Gareth D. H. Turner,
- Colin Clelland,
- Jeongmin Woo,
- Amy Cross,
- Fadi Issa,
- Carlos Eduardo de Andrea,
- Ignacio Melero Bermejo,
- David Sims,
- Simon McGowan,
- Yasemin-Xiomara Zurke,
- David J. Ahern,
- Eddie C. Gamez,
- Justin Whalley,
- Duncan Richards,
- Paul Klenerman,
- Claudia Monaco,
- Irina A. Udalova,
- Tao Dong,
- Agne Antanaviciute,
- Graham Ogg,
- Julian C. Knight,
- Helen M. Byrne,
- Stephen Taylor,
- Ling-Pei Ho
Affiliations
- Praveen Weeratunga
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Laura Denney
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Joshua A. Bull
- Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford
- Emmanouela Repapi
- MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Martin Sergeant
- MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Rachel Etherington
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Chaitanya Vuppussetty
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Gareth D. H. Turner
- Department of Cellular Pathology and Radcliffe Department of Medicine, Oxford University Hospitals NHS Foundation Trust
- Colin Clelland
- Anatomic Pathology, Weill Cornell Medical College
- Jeongmin Woo
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Amy Cross
- Nuffield Department of Surgical Sciences, University of Oxford
- Fadi Issa
- Nuffield Department of Surgical Sciences, University of Oxford
- Carlos Eduardo de Andrea
- Navarra Institute for Health Research
- Ignacio Melero Bermejo
- Navarra Institute for Health Research
- David Sims
- MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Simon McGowan
- MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Yasemin-Xiomara Zurke
- Kennedy Institute for Rheumatology, University of Oxford
- David J. Ahern
- Kennedy Institute for Rheumatology, University of Oxford
- Eddie C. Gamez
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
- Justin Whalley
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
- Duncan Richards
- Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Diseases, University of Oxford
- Paul Klenerman
- Nuffield Department of Medicine, University of Oxford
- Claudia Monaco
- Kennedy Institute for Rheumatology, University of Oxford
- Irina A. Udalova
- Kennedy Institute for Rheumatology, University of Oxford
- Tao Dong
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Agne Antanaviciute
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Graham Ogg
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Julian C. Knight
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford
- Helen M. Byrne
- Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford
- Stephen Taylor
- MRC WIMM Computational Biology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Ling-Pei Ho
- MRC Translational Immunology Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- DOI
- https://doi.org/10.1038/s41467-023-42421-0
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 20
Abstract
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.
