tetano
Editor, Senior Moderator
Front Immunol
. 2022 Nov 17;13:1039120.
doi: 10.3389/fimmu.2022.1039120. eCollection 2022.
Age-dependent NK cell dysfunctions in severe COVID-19 patients
Cinzia Fionda[SUP] 1 2 [/SUP], Silvia Ruggeri[SUP] 1 2 [/SUP], Giuseppe Sciumè[SUP] 1 2 [/SUP], Mattia Laffranchi[SUP] 1 2 [/SUP], Isabella Quinti[SUP] 1 [/SUP], Cinzia Milito[SUP] 1 [/SUP], Paolo Palange[SUP] 3 [/SUP], Ilaria Menichini[SUP] 3 [/SUP], Silvano Sozzani[SUP] 1 2 4 [/SUP], Luigi Frati[SUP] 1 2 4 [/SUP], Angela Gismondi[SUP] 1 2 [/SUP], Angela Santoni[SUP] 1 2 4 [/SUP], Helena Stabile[SUP] 1 2 [/SUP]
Affiliations
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 CD56[SUP]low[/SUP]CD16[SUP]high[/SUP] and CD56[SUP]neg[/SUP] 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.
Keywords: COVID-19; NK cell subsets; Natural Killer cells; T-BET; TGF-β; ageing; inflammation.
. 2022 Nov 17;13:1039120.
doi: 10.3389/fimmu.2022.1039120. eCollection 2022.
Age-dependent NK cell dysfunctions in severe COVID-19 patients
Cinzia Fionda[SUP] 1 2 [/SUP], Silvia Ruggeri[SUP] 1 2 [/SUP], Giuseppe Sciumè[SUP] 1 2 [/SUP], Mattia Laffranchi[SUP] 1 2 [/SUP], Isabella Quinti[SUP] 1 [/SUP], Cinzia Milito[SUP] 1 [/SUP], Paolo Palange[SUP] 3 [/SUP], Ilaria Menichini[SUP] 3 [/SUP], Silvano Sozzani[SUP] 1 2 4 [/SUP], Luigi Frati[SUP] 1 2 4 [/SUP], Angela Gismondi[SUP] 1 2 [/SUP], Angela Santoni[SUP] 1 2 4 [/SUP], Helena Stabile[SUP] 1 2 [/SUP]
Affiliations
- PMID: 36466890
- PMCID: PMC9713640
- DOI: 10.3389/fimmu.2022.1039120
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 CD56[SUP]low[/SUP]CD16[SUP]high[/SUP] and CD56[SUP]neg[/SUP] 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.
Keywords: COVID-19; NK cell subsets; Natural Killer cells; T-BET; TGF-β; ageing; inflammation.