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Age-dependent NK cell dysfunctions in severe COVID-19 patients.

Authors :: Fionda C
Ruggeri S
Sciumè G
Laffranchi M
Quinti I
Milito C
Palange P
Menichini I
Sozzani S
Frati L
Gismondi A
Santoni A
Stabile H
Source :: Frontiers in immunology [Front Immunol] 2022 Nov 17; Vol. 13, pp. 1039120. Date of Electronic Publication: 2022 Nov 17 (Print Publication: 2022).
Publication Year :: 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 CD56 <superscript>low</superscript> CD16 <superscript>high</superscript> and CD56 <superscript>neg</superscript> 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.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2022 Fionda, Ruggeri, Sciumè, Laffranchi, Quinti, Milito, Palange, Menichini, Sozzani, Frati, Gismondi, Santoni and Stabile.)