Cargando…
Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls
Severe respiratory viral infections, including SARS-CoV-2, have resulted in high mortality rates despite corticosteroids and other immunomodulatory therapies. Despite recognition of the pathogenic role of neutrophils, in-depth analyses of this cell population have been limited, due to technical chal...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709423/ https://www.ncbi.nlm.nih.gov/pubmed/36466858 http://dx.doi.org/10.3389/fimmu.2022.970287 |
_version_ | 1784841151745884160 |
---|---|
author | Xu, Jintao He, Bing Carver, Kyle Vanheyningen, Debora Parkin, Brian Garmire, Lana X. Olszewski, Michal A. Deng, Jane C. |
author_facet | Xu, Jintao He, Bing Carver, Kyle Vanheyningen, Debora Parkin, Brian Garmire, Lana X. Olszewski, Michal A. Deng, Jane C. |
author_sort | Xu, Jintao |
collection | PubMed |
description | Severe respiratory viral infections, including SARS-CoV-2, have resulted in high mortality rates despite corticosteroids and other immunomodulatory therapies. Despite recognition of the pathogenic role of neutrophils, in-depth analyses of this cell population have been limited, due to technical challenges of working with neutrophils. We undertook an unbiased, detailed analysis of neutrophil responses in adult patients with COVID-19 and healthy controls, to determine whether distinct neutrophil phenotypes could be identified during infections compared to the healthy state. Single-cell RNA sequencing analysis of peripheral blood neutrophils from hospitalized patients with mild or severe COVID-19 disease and healthy controls revealed distinct mature neutrophil subpopulations, with relative proportions linked to disease severity. Disruption of predicted cell-cell interactions, activated oxidative phosphorylation genes, and downregulated antiviral and host defense pathway genes were observed in neutrophils obtained during severe compared to mild infections. Our findings suggest that during severe infections, there is a loss of normal regulatory neutrophil phenotypes seen in healthy subjects, coupled with the dropout of appropriate cellular interactions. Given that neutrophils are the most abundant circulating leukocytes with highly pathogenic potential, current immunotherapies for severe infections may be optimized by determining whether they aid in restoring an appropriate balance of neutrophil subpopulations. |
format | Online Article Text |
id | pubmed-9709423 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97094232022-12-01 Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls Xu, Jintao He, Bing Carver, Kyle Vanheyningen, Debora Parkin, Brian Garmire, Lana X. Olszewski, Michal A. Deng, Jane C. Front Immunol Immunology Severe respiratory viral infections, including SARS-CoV-2, have resulted in high mortality rates despite corticosteroids and other immunomodulatory therapies. Despite recognition of the pathogenic role of neutrophils, in-depth analyses of this cell population have been limited, due to technical challenges of working with neutrophils. We undertook an unbiased, detailed analysis of neutrophil responses in adult patients with COVID-19 and healthy controls, to determine whether distinct neutrophil phenotypes could be identified during infections compared to the healthy state. Single-cell RNA sequencing analysis of peripheral blood neutrophils from hospitalized patients with mild or severe COVID-19 disease and healthy controls revealed distinct mature neutrophil subpopulations, with relative proportions linked to disease severity. Disruption of predicted cell-cell interactions, activated oxidative phosphorylation genes, and downregulated antiviral and host defense pathway genes were observed in neutrophils obtained during severe compared to mild infections. Our findings suggest that during severe infections, there is a loss of normal regulatory neutrophil phenotypes seen in healthy subjects, coupled with the dropout of appropriate cellular interactions. Given that neutrophils are the most abundant circulating leukocytes with highly pathogenic potential, current immunotherapies for severe infections may be optimized by determining whether they aid in restoring an appropriate balance of neutrophil subpopulations. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9709423/ /pubmed/36466858 http://dx.doi.org/10.3389/fimmu.2022.970287 Text en Copyright © 2022 Xu, He, Carver, Vanheyningen, Parkin, Garmire, Olszewski and Deng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Xu, Jintao He, Bing Carver, Kyle Vanheyningen, Debora Parkin, Brian Garmire, Lana X. Olszewski, Michal A. Deng, Jane C. Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls |
title | Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls |
title_full | Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls |
title_fullStr | Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls |
title_full_unstemmed | Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls |
title_short | Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls |
title_sort | heterogeneity of neutrophils and inflammatory responses in patients with covid-19 and healthy controls |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709423/ https://www.ncbi.nlm.nih.gov/pubmed/36466858 http://dx.doi.org/10.3389/fimmu.2022.970287 |
work_keys_str_mv | AT xujintao heterogeneityofneutrophilsandinflammatoryresponsesinpatientswithcovid19andhealthycontrols AT hebing heterogeneityofneutrophilsandinflammatoryresponsesinpatientswithcovid19andhealthycontrols AT carverkyle heterogeneityofneutrophilsandinflammatoryresponsesinpatientswithcovid19andhealthycontrols AT vanheyningendebora heterogeneityofneutrophilsandinflammatoryresponsesinpatientswithcovid19andhealthycontrols AT parkinbrian heterogeneityofneutrophilsandinflammatoryresponsesinpatientswithcovid19andhealthycontrols AT garmirelanax heterogeneityofneutrophilsandinflammatoryresponsesinpatientswithcovid19andhealthycontrols AT olszewskimichala heterogeneityofneutrophilsandinflammatoryresponsesinpatientswithcovid19andhealthycontrols AT dengjanec heterogeneityofneutrophilsandinflammatoryresponsesinpatientswithcovid19andhealthycontrols |