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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.970287/full |
| _version_ | 1828290825240444928 |
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| author | Jintao Xu Jintao Xu Bing He Kyle Carver Kyle Carver Debora Vanheyningen Debora Vanheyningen Brian Parkin Brian Parkin Lana X. Garmire Michal A. Olszewski Michal A. Olszewski Jane C. Deng Jane C. Deng |
| author_facet | Jintao Xu Jintao Xu Bing He Kyle Carver Kyle Carver Debora Vanheyningen Debora Vanheyningen Brian Parkin Brian Parkin Lana X. Garmire Michal A. Olszewski Michal A. Olszewski Jane C. Deng Jane C. Deng |
| author_sort | Jintao Xu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T10:42:02Z |
| format | Article |
| id | doaj.art-fd2f2bc0be214cf0b370425530462fc4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T10:42:02Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fd2f2bc0be214cf0b370425530462fc42022-12-22T02:49:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.970287970287Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controlsJintao Xu0Jintao Xu1Bing He2Kyle Carver3Kyle Carver4Debora Vanheyningen5Debora Vanheyningen6Brian Parkin7Brian Parkin8Lana X. Garmire9Michal A. Olszewski10Michal A. Olszewski11Jane C. Deng12Jane C. Deng13Research Service, LTC Charles S. Kettles Veterans Affairs Medical Center, Department of Veterans Affairs Health System, Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United StatesResearch Service, LTC Charles S. Kettles Veterans Affairs Medical Center, Department of Veterans Affairs Health System, Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United StatesResearch Service, LTC Charles S. Kettles Veterans Affairs Medical Center, Department of Veterans Affairs Health System, Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United StatesResearch Service, LTC Charles S. Kettles Veterans Affairs Medical Center, Department of Veterans Affairs Health System, Ann Arbor, MI, United StatesDivision of Hematology and Oncology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, United StatesDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United StatesResearch Service, LTC Charles S. Kettles Veterans Affairs Medical Center, Department of Veterans Affairs Health System, Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United StatesResearch Service, LTC Charles S. Kettles Veterans Affairs Medical Center, Department of Veterans Affairs Health System, Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United StatesSevere 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.970287/fullCOVID-19immune responsesingle-cell sequencingneutrophil heterogeneitySARS – CoV – 2 |
| spellingShingle | Jintao Xu Jintao Xu Bing He Kyle Carver Kyle Carver Debora Vanheyningen Debora Vanheyningen Brian Parkin Brian Parkin Lana X. Garmire Michal A. Olszewski Michal A. Olszewski Jane C. Deng Jane C. Deng Heterogeneity of neutrophils and inflammatory responses in patients with COVID-19 and healthy controls Frontiers in Immunology COVID-19 immune response single-cell sequencing neutrophil heterogeneity SARS – CoV – 2 |
| 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 | COVID-19 immune response single-cell sequencing neutrophil heterogeneity SARS – CoV – 2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.970287/full |
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