Journal Article

Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications

Terzoli, Sara, Della Bella, Silvia, Mavilio, Domenico, Calcaterra, Francesca, Mikulak, Joanna, Coianiz, Nicolò, Voza, Antonio, Di Vito, Clara

2022

Overview

Natural Killer (NK) cells are lymphocytes of the innate immunity that play a crucial role in the control of viral infections in the absence of a prior antigen sensitization. Indeed, they display rapid effector functions against target cells with the capability of direct cell killing and antibody-dependent cell-mediated cytotoxicity. Furthermore, NK cells are endowed with immune-modulatory functions innate and adaptive immune responses via the secretion of chemokines/cytokines and by undertaking synergic crosstalks with other innate immune cells, including monocyte/macrophages, dendritic cells and neutrophils. Recently, the Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the specific role of NK cells in COVID-19 pathophysiology still need to be explored, mounting evidence indicates that NK cell tissue distribution and effector functions could be affected by SARS-CoV-2 infection and that a prompt NK cell response could determine a good clinical outcome in COVID-19 patients. In this review, we give a comprehensive overview of how SARS-CoV-2 infection interferes with NK cell antiviral effectiveness and their crosstalk with other innate immune cells. We also provide a detailed characterization of the specific NK cell subsets in relation to COVID-19 patient severity generated from publicly available single cell RNA sequencing datasets. Finally, we summarize the possible NK cell-based therapeutic approaches against SARS-CoV-2 infection and the ongoing clinical trials updated at the time of submission of this review. We will also discuss how a deep understanding of NK cell responses could open new possibilities for the treatment and prevention of SARS-CoV-2 infection.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Antibody-dependent cell-mediated cytotoxicity / Chemokines / Clinical trials / Coronaviruses / COVID-19 / Cytotoxicity / Dendritic cells / Effector cells / Immunology / Immunomodulation / immunotherapy / Innate immunity / Leukocytes (neutrophilic) / Lymphocytes / Macrophages / memory-like / Monocytes / Natural killer cells / NK cells / Pathophysiology / Patients / SARS-CoV-2 infection / Severe acute respiratory syndrome coronavirus 2 / single cell sequencing / Tumor necrosis factor-TNF / Viral infections / Viruses