Rhinovirus infection modulates MHC class I-related chain A and B molecules in human respiratory epithelial cells (133.37)

Abstract

Abstract Cell surface and soluble MICA and MICB molecules induced by stress/viruses could activate, respectively impair, cytotoxic activity of NKG2D+ NK and CD8 T cells. We hypothesised that rhinovirus (RV) infection of bronchial epithelial cells alters the balance between activatory (surface) and inhibitory (soluble) MICA and MICB molecule. MIC molecules were investigated in BEAS-2B cells (a bronchial epithelial cell line) exposed in vitro to RV1B MOI 1 ± IL-4 10ng/ml up to 72 hours by flow cytometry (intracellular and cell surface) and ELISA (soluble molecules in supernatants). RV1B infection of BEAS-2B cells increased the levels of surface MICA in a dose- and replication-dependent manner, peaking at 24h and gradually decreased during 72h. RV1B-induced soluble MICA molecule levels increased in a time-dependent manner, peaking at 72h. IL-4 presence during RV1B infection increased RV1B-iduced surface MICA (MFI: 72±9 versus 45±10, p<0.05) and soluble MICA levels (12±8 versus 9±7, p=0.3). Intracellular and surface MICB molecules were decreased by RV1B infection and IL-4 further decreased intracellular levels. To conclude, RV1B infection in BEAS-2B cells in the presence of IL-4 up-regulated the surface MICA levels but also increased soluble MICA levels which could inhibit in vivo the activation of NKG2D+ cells and by doing this delaying virus clearance and prolonging the airway inflammation in virus-induced asthma.