NK cells: A double edge sword against SARS-CoV-2

Abstract

Natural killer (NK) cells are pivotal effectors of the innate immunity protecting an individual from microbes. They are the first line of defense against invading viruses, given their substantial ability to directly target infected cells without the need for specific antigen presentation. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify and modulate antiviral adaptive immune responses. In this review, we will examine the role of NK cells in SARS-COV2 infections causing the ongoing COVID19 pandemic, keeping in mind the controversial role of NK cells specifically in viral respiratory infections and in inflammatory-driven lung damage. We discuss lessons learnt from previous coronavirus outbreaks in humans (caused by SARS-CoV-1 and MERS-COV).

Keywords: COVID-19; Lung inflammation; NK cells; Viral infection.

Fig. 1

Hypothesized double-sided mechanism of Sars-Cov-2 and NK cells interaction. In case of effective immune innate response, NK cells express the activation marker CD107a and release IFNɣ, IL-2, and TNFɑ (right side). In case of exhaustion, NK cells overexpress the inhibitory NKG2A receptor, which suppress T-cell and NK cytotoxic function, favoring a pro-inflammatory condition (left side).

Fig. 2

Hypothesized opposite behavior of circulating vs. lung-resident NK cells during COVID-19: NK cells that remain in the circulation display an exhausted phenotype that facilitate virus spread while NK cells that exit blood and traffic into the lung contribute to local inflammation and tissue damage.