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Organ‐specific immune response in lethal SARS‐CoV‐2 infection by deep spatial phenotyping

OBJECTIVES: Immunopathology of ongoing COVID‐19 global pandemic is not limited solely to pulmonary tissue, but is often associated with multi‐organ complications, mechanisms of which are intensely being investigated. In this regard, the interplay between immune, stromal cells and cytokines in pulmon...

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Autores principales: Balachander, Akhila, Lee, Bernett, Biswas, Subhra K, Lye, David C, Lin, Raymond TP, Leo, Yee‐Sin, Chui, Paul, Ng, Lisa FP, Renia, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108111/
https://www.ncbi.nlm.nih.gov/pubmed/35602886
http://dx.doi.org/10.1002/cti2.1384
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author Balachander, Akhila
Lee, Bernett
Biswas, Subhra K
Lye, David C
Lin, Raymond TP
Leo, Yee‐Sin
Chui, Paul
Ng, Lisa FP
Renia, Laurent
author_facet Balachander, Akhila
Lee, Bernett
Biswas, Subhra K
Lye, David C
Lin, Raymond TP
Leo, Yee‐Sin
Chui, Paul
Ng, Lisa FP
Renia, Laurent
author_sort Balachander, Akhila
collection PubMed
description OBJECTIVES: Immunopathology of ongoing COVID‐19 global pandemic is not limited solely to pulmonary tissue, but is often associated with multi‐organ complications, mechanisms of which are intensely being investigated. In this regard, the interplay between immune, stromal cells and cytokines in pulmonary and extrapulmonary infected tissues, especially in young adults (median age 46 years, range 30–53 years) without comorbidities, remains poorly characterised. METHODS: We profiled lung, heart and intestinal autopsy samples from five SARS‐CoV‐2‐infected cases for 18–20 targets to detect immune, cytokine and stromal cell status at subcellular resolution by a novel IHC‐based deep‐phenotyping technique, iSPOT (immunoSpatial histoPhenOmics using TSA‐IHC), to assess spatial and functional patterns of immune response in situ, in lethal COVID‐19 infection. RESULTS: SARS‐CoV‐2‐infected autopsy samples exhibit skewed counts of immune populations in all samples with organ‐specific dysfunctions. Lung and ileal tissue reveal altered architecture with marked loss of tissue integrity, while lung and heart tissue show severe hyperinflammation marked by elevated TNF‐α in heart tissue and additionally IL‐6, IFN‐γ and IL‐10 cytokines in lung samples. CONCLUSION: With resurgence of infection in younger populations, single‐cell cytokine localisation in immune and stromal structures provides important mechanistic insights into organ‐specific immunopathology of naïve SARS‐CoV‐2 infection in the absence of other comorbidities.
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spelling pubmed-91081112022-05-20 Organ‐specific immune response in lethal SARS‐CoV‐2 infection by deep spatial phenotyping Balachander, Akhila Lee, Bernett Biswas, Subhra K Lye, David C Lin, Raymond TP Leo, Yee‐Sin Chui, Paul Ng, Lisa FP Renia, Laurent Clin Transl Immunology Short Communications OBJECTIVES: Immunopathology of ongoing COVID‐19 global pandemic is not limited solely to pulmonary tissue, but is often associated with multi‐organ complications, mechanisms of which are intensely being investigated. In this regard, the interplay between immune, stromal cells and cytokines in pulmonary and extrapulmonary infected tissues, especially in young adults (median age 46 years, range 30–53 years) without comorbidities, remains poorly characterised. METHODS: We profiled lung, heart and intestinal autopsy samples from five SARS‐CoV‐2‐infected cases for 18–20 targets to detect immune, cytokine and stromal cell status at subcellular resolution by a novel IHC‐based deep‐phenotyping technique, iSPOT (immunoSpatial histoPhenOmics using TSA‐IHC), to assess spatial and functional patterns of immune response in situ, in lethal COVID‐19 infection. RESULTS: SARS‐CoV‐2‐infected autopsy samples exhibit skewed counts of immune populations in all samples with organ‐specific dysfunctions. Lung and ileal tissue reveal altered architecture with marked loss of tissue integrity, while lung and heart tissue show severe hyperinflammation marked by elevated TNF‐α in heart tissue and additionally IL‐6, IFN‐γ and IL‐10 cytokines in lung samples. CONCLUSION: With resurgence of infection in younger populations, single‐cell cytokine localisation in immune and stromal structures provides important mechanistic insights into organ‐specific immunopathology of naïve SARS‐CoV‐2 infection in the absence of other comorbidities. John Wiley and Sons Inc. 2022-05-15 /pmc/articles/PMC9108111/ /pubmed/35602886 http://dx.doi.org/10.1002/cti2.1384 Text en © 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Short Communications
Balachander, Akhila
Lee, Bernett
Biswas, Subhra K
Lye, David C
Lin, Raymond TP
Leo, Yee‐Sin
Chui, Paul
Ng, Lisa FP
Renia, Laurent
Organ‐specific immune response in lethal SARS‐CoV‐2 infection by deep spatial phenotyping
title Organ‐specific immune response in lethal SARS‐CoV‐2 infection by deep spatial phenotyping
title_full Organ‐specific immune response in lethal SARS‐CoV‐2 infection by deep spatial phenotyping
title_fullStr Organ‐specific immune response in lethal SARS‐CoV‐2 infection by deep spatial phenotyping
title_full_unstemmed Organ‐specific immune response in lethal SARS‐CoV‐2 infection by deep spatial phenotyping
title_short Organ‐specific immune response in lethal SARS‐CoV‐2 infection by deep spatial phenotyping
title_sort organ‐specific immune response in lethal sars‐cov‐2 infection by deep spatial phenotyping
topic Short Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108111/
https://www.ncbi.nlm.nih.gov/pubmed/35602886
http://dx.doi.org/10.1002/cti2.1384
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