The Promise and Peril of Natural Killer Cell Therapies in Pulmonary Infection

At low to intermediate inoculum doses of respiratory syncytial virus (RSV), Sendai virus (parainfluenza virus), and influenza A virus (IAV) infections in mice and hamsters, the activities of NK cells can reduce viral burden and protect from fatal disease (Cong and Wei, 2019). Exuberant NK-cell activity, including IFN-γ production, contributes to this aggravated lung inflammation during both IAV and RSV infections (Cong and Wei, 2019; Li et al., 2012; Abdul-Careem et al., 2012). [...]elevated IL-2 and IL-18 amplify these pathological activities of NK cells during these infections and promote interstitial pneumonia (Okamoto et al., 2002; Harker et al., 2010; McKinstry et al., 2019). [...]while hopes remain high that the potent antiviral functionality of these NK cells will provide clinical benefit, the potential for damage to the lungs, liver, and kidneys should be serious concerns and monitored very carefully in these trials.