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

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

doi:10.3389/fimmu.2022.1039120

Frontiers in Immunology (Nov 2022)

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

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

Affiliations

Cinzia Fionda: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Cinzia Fionda: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
Silvia Ruggeri: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Silvia Ruggeri: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
Giuseppe Sciumè: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Giuseppe Sciumè: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
Mattia Laffranchi: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Mattia Laffranchi: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
Isabella Quinti: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Cinzia Milito: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Paolo Palange: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
Ilaria Menichini: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
Silvano Sozzani: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Silvano Sozzani: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
Silvano Sozzani: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Neuromed, Pozzilli, Italy
Luigi Frati: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Luigi Frati: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
Luigi Frati: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Neuromed, Pozzilli, Italy
Angela Gismondi: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Angela Gismondi: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
Angela Santoni: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Angela Santoni: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy
Angela Santoni: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Neuromed, Pozzilli, Italy
Helena Stabile: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
Helena Stabile: Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy

DOI: https://doi.org/10.3389/fimmu.2022.1039120
Journal volume & issue: Vol. 13

Abstract

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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.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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