Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1039120
Keywords
Natural Killer cells; NK cell subsets; COVID-19; ageing; inflammation; T-BET; TGF-beta
Categories
Funding
- Ministero dell'Istruzione, dell'Universita e della Ricerca [COVID-2020-12371735-Neuromed]
- [RM12117A5D5C4A0E]
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In this study, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infection. The results showed that elderly patients had altered NK cell subsets, with a higher activation level compared to adult 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 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(low)CD16(high) and CD56(neg) phenotypes, expressing activation markers and check-point inhibitory receptors. Although NK cell degranulation ability is significantly compromised in both cohorts, IFN-gamma production is impaired only in adult patients in a TGF-beta-dependent manner. This inhibitory effect was associated with a shorter hospitalization time of adult patients suggesting a role for TGF-beta 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.
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