Age-dependent NK cell dysfunctions in severe COVID-19 patients
Natural Killer (NK) cells are key innate effectors of antiviral immune response, and their activity changes in ageing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infectio...
| 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 |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1039120/full |
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| author | Cinzia Fionda Cinzia Fionda Silvia Ruggeri Silvia Ruggeri Giuseppe Sciumè Giuseppe Sciumè Mattia Laffranchi Mattia Laffranchi Isabella Quinti Cinzia Milito Paolo Palange Ilaria Menichini Silvano Sozzani Silvano Sozzani Silvano Sozzani Luigi Frati Luigi Frati Luigi Frati Angela Gismondi Angela Gismondi Angela Santoni Angela Santoni Angela Santoni Helena Stabile Helena Stabile |
| author_facet | Cinzia Fionda Cinzia Fionda Silvia Ruggeri Silvia Ruggeri Giuseppe Sciumè Giuseppe Sciumè Mattia Laffranchi Mattia Laffranchi Isabella Quinti Cinzia Milito Paolo Palange Ilaria Menichini Silvano Sozzani Silvano Sozzani Silvano Sozzani Luigi Frati Luigi Frati Luigi Frati Angela Gismondi Angela Gismondi Angela Santoni Angela Santoni Angela Santoni Helena Stabile Helena Stabile |
| author_sort | Cinzia Fionda |
| collection | DOAJ |
| description | Natural Killer (NK) cells are key innate effectors of antiviral immune response, and their activity changes in ageing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infection, by comparing adult and elderly patients both requiring mechanical ventilation. Adult patients had a reduced number of total NK cells, while elderly showed a peculiar skewing of NK cell subsets towards the CD56lowCD16high and CD56neg phenotypes, expressing activation markers and check-point inhibitory receptors. Although NK cell degranulation ability is significantly compromised in both cohorts, IFN-γ production is impaired only in adult patients in a TGF-β−dependent manner. This inhibitory effect was associated with a shorter hospitalization time of adult patients suggesting a role for TGF-β in preventing an excessive NK cell activation and systemic inflammation. Our data highlight an age-dependent role of NK cells in shaping SARS-CoV-2 infection toward a pathophysiological evolution. |
| first_indexed | 2024-04-12T08:49:54Z |
| format | Article |
| id | doaj.art-dd4ab049a2bf4e2a95d219e4f52c73fd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T08:49:54Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dd4ab049a2bf4e2a95d219e4f52c73fd2022-12-22T03:39:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10391201039120Age-dependent NK cell dysfunctions in severe COVID-19 patientsCinzia Fionda0Cinzia Fionda1Silvia Ruggeri2Silvia Ruggeri3Giuseppe Sciumè4Giuseppe Sciumè5Mattia Laffranchi6Mattia Laffranchi7Isabella Quinti8Cinzia Milito9Paolo Palange10Ilaria Menichini11Silvano Sozzani12Silvano Sozzani13Silvano Sozzani14Luigi Frati15Luigi Frati16Luigi Frati17Angela Gismondi18Angela Gismondi19Angela Santoni20Angela Santoni21Angela Santoni22Helena Stabile23Helena Stabile24Department of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Neuromed, Pozzilli, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Neuromed, Pozzilli, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Neuromed, Pozzilli, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Rome, ItalyNatural Killer (NK) cells are key innate effectors of antiviral immune response, and their activity changes in ageing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infection, by comparing adult and elderly patients both requiring mechanical ventilation. Adult patients had a reduced number of total NK cells, while elderly showed a peculiar skewing of NK cell subsets towards the CD56lowCD16high and CD56neg phenotypes, expressing activation markers and check-point inhibitory receptors. Although NK cell degranulation ability is significantly compromised in both cohorts, IFN-γ production is impaired only in adult patients in a TGF-β−dependent manner. This inhibitory effect was associated with a shorter hospitalization time of adult patients suggesting a role for TGF-β in preventing an excessive NK cell activation and systemic inflammation. Our data highlight an age-dependent role of NK cells in shaping SARS-CoV-2 infection toward a pathophysiological evolution.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1039120/fullNatural Killer cellsNK cell subsetsCOVID-19ageinginflammationT-BET |
| spellingShingle | Cinzia Fionda Cinzia Fionda Silvia Ruggeri Silvia Ruggeri Giuseppe Sciumè Giuseppe Sciumè Mattia Laffranchi Mattia Laffranchi Isabella Quinti Cinzia Milito Paolo Palange Ilaria Menichini Silvano Sozzani Silvano Sozzani Silvano Sozzani Luigi Frati Luigi Frati Luigi Frati Angela Gismondi Angela Gismondi Angela Santoni Angela Santoni Angela Santoni Helena Stabile Helena Stabile Age-dependent NK cell dysfunctions in severe COVID-19 patients Frontiers in Immunology Natural Killer cells NK cell subsets COVID-19 ageing inflammation T-BET |
| title | Age-dependent NK cell dysfunctions in severe COVID-19 patients |
| title_full | Age-dependent NK cell dysfunctions in severe COVID-19 patients |
| title_fullStr | Age-dependent NK cell dysfunctions in severe COVID-19 patients |
| title_full_unstemmed | Age-dependent NK cell dysfunctions in severe COVID-19 patients |
| title_short | Age-dependent NK cell dysfunctions in severe COVID-19 patients |
| title_sort | age dependent nk cell dysfunctions in severe covid 19 patients |
| topic | Natural Killer cells NK cell subsets COVID-19 ageing inflammation T-BET |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1039120/full |
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