The upregulation of peripheral CD3-CD56+CD16+ natural killer cells correlates with Th1/Th2 imbalance in asthma patients during acute upper respiratory viral infections

Abstract

Abstract Purpose The aim of this study is to clarify the changes of peripheral CD3−CD56+CD16+ NK cells and their correlation with Th1/Th2 immunity profiles in asthma during the phase of acute upper respiratory viral infections (AURVIs). Methods Peripheral venous blood and induced sputum samples were collected from 56 mild asthma patients, 49 asthma patients with AURVIs and 50 healthy subjects. Peripheral CD3−CD56+CD16+ NK cells were monitored by flow cytometry during the course of acute viral infections. Meanwhile, the induced sputum Th2 cytokines IL-4 and IL-5, and Th1 cytokine IFN-γ were also detected by ELISA assay. Results The asthmatics had lower levels of peripheral CD3−CD56+CD16+ NK cells populations as well as higher induced sputum cytokines (IL-4, IL-5 and IFN-γ) compared to healthy controls at baseline. Upon upper respiratory viral infections, peripheral CD3−CD56+CD16+ NK cells numbers in asthma patients sharply elevated on day 3 and slowly decreased by day 14, in accordance with induced sputum IFN-γ changes. IL-4 and IL-5 levels spiked much later (day 8) and lasted until day 14. Compared with asthma alone group, the IFN-γ/IL-4 and IFN-γ/IL-5 ratios of the asthma patients with AURVIs on day 1 were higher and peaked on day 3. The changes of peripheral CD3−CD56+CD16+ NK cells proportions positively correlated with the IFN-γ/IL-4 and IFN-γ/IL-5 ratios on day 1 to day 3 in asthma subsequent to upper respiratory viral infections. Conclusions Our findings showed an imbalanced Th1/Th2 immunity in airways of asthma with acute upper respiratory viral infections. Upregulated peripheral CD3−CD56+CD16+ NK cells play a crucial role in biased Th1 immunity of airways in asthma during the acute phase of viral infections. The anti-viral Th1 immunity by targeting NK cells may be a possible therapeutic option for virus-induced asthma exacerbation.