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.
Age-dependent NK cell dysfunctions in severe COVID-19 patients / Fionda, Cinzia; Ruggeri, Silvia; Sciume', Giuseppe; Laffranchi, Mattia; Quinti, Isabella; Milito, Cinzia; Palange, Paolo; Menichini, Ilaria; Sozzani, Silvano; Frati, Luigi; Gismondi, Angela; Santoni, Angela; Stabile, MARIA HELENA. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 13:(2022), pp. 1-19. [10.3389/fimmu.2022.1039120]
Age-dependent NK cell dysfunctions in severe COVID-19 patients
Cinzia Fionda;Silvia Ruggeri;Giuseppe Sciume;Mattia Laffranchi;Isabella Quinti;Cinzia Milito;Paolo Palange;Ilaria Menichini;Silvano Sozzani;Luigi Frati;Angela Gismondi;Angela Santoni
;Helena Stabile.
2022
Abstract
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.File | Dimensione | Formato | |
---|---|---|---|
Fionda_Age-dependent_2022.pdf
accesso aperto
Note: Articolo in rivista
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Creative commons
Dimensione
7.51 MB
Formato
Adobe PDF
|
7.51 MB | Adobe PDF | Visualizza/Apri PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.