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Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs

Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs
Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs

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.

2041-1723
Weeratunga, Praveen
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Denney, Laura
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Bull, Joshua A.
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Repapi, Emmanouela
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Sergeant, Martin
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Etherington, Rachel
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Vuppussetty, Chaitanya
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Turner, Gareth D.H.
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Clelland, Colin
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Woo, Jeongmin
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Cross, Amy
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Issa, Fadi
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de Andrea, Carlos Eduardo
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Melero Bermejo, Ignacio
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McGowan, Simon
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Zurke, Yasemin Xiomara
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Ahern, David J.
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Gamez, Eddie C.
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Whalley, Justin
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Richards, Duncan
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Klenerman, Paul
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Monaco, Claudia
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Udalova, Irina A.
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Dong, Tao
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Antanaviciute, Agne
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Ogg, Graham
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Knight, Julian C.
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Byrne, Helen M.
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Taylor, Stephen
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Ho, Ling Pei
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Weeratunga, Praveen
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Denney, Laura
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Bull, Joshua A.
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Repapi, Emmanouela
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Sergeant, Martin
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Etherington, Rachel
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Vuppussetty, Chaitanya
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Turner, Gareth D.H.
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Clelland, Colin
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Woo, Jeongmin
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Cross, Amy
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Issa, Fadi
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de Andrea, Carlos Eduardo
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Melero Bermejo, Ignacio
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McGowan, Simon
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Zurke, Yasemin Xiomara
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Ahern, David J.
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Gamez, Eddie C.
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Whalley, Justin
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Richards, Duncan
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Klenerman, Paul
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Monaco, Claudia
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Udalova, Irina A.
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Dong, Tao
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Antanaviciute, Agne
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Ogg, Graham
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Knight, Julian C.
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Byrne, Helen M.
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Taylor, Stephen
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Ho, Ling Pei
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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, 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 and Ho, Ling Pei (2023) Single cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs. Nature Communications, [7216]. (doi:10.1038/s41467-023-42421-0).

Record type: Article

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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s41467-023-42421-0 - Version of Record
Available under License Creative Commons Attribution.
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More information

Accepted/In Press date: 11 October 2023
Published date: 8 November 2023

Identifiers

Local EPrints ID: 494167
URI: http://eprints.soton.ac.uk/id/eprint/494167
DOI: doi:10.1038/s41467-023-42421-0
ISSN: 2041-1723
PURE UUID: 1e508649-9a48-4377-96c4-7296fa254c49
ORCID for Stephen Taylor: ORCID iD orcid.org/0000-0002-9937-1762

Catalogue record

Date deposited: 26 Sep 2024 16:45
Last modified: 01 Oct 2024 01:36

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Contributors

Author: Praveen Weeratunga
Author: Laura Denney
Author: Joshua A. Bull
Author: Emmanouela Repapi
Author: Martin Sergeant
Author: Rachel Etherington
Author: Chaitanya Vuppussetty
Author: Gareth D.H. Turner
Author: Colin Clelland
Author: Jeongmin Woo
Author: Amy Cross
Author: Fadi Issa
Author: Carlos Eduardo de Andrea
Author: Ignacio Melero Bermejo
Author: Simon McGowan
Author: Yasemin Xiomara Zurke
Author: David J. Ahern
Author: Eddie C. Gamez
Author: Justin Whalley
Author: Duncan Richards
Author: Paul Klenerman
Author: Claudia Monaco
Author: Irina A. Udalova
Author: Tao Dong
Author: Agne Antanaviciute
Author: Graham Ogg
Author: Julian C. Knight
Author: Helen M. Byrne
Author: Stephen Taylor ORCID iD
Author: Ling Pei Ho

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