KIR2DL2 overexpression influences NK cell response to CpG.

NK cells are innate effectors towards viral infections, sensing viral unmethylated CpG motifs (CpG-ODN) through TLR9. NK cell activation is controlled by killer-cell inhibitory and activating receptors (KIR, KAR). Rizzo et al. [J Neuroimmunol 2012] reported that a 40% Multiple Sclerosis (MS) patients were unable to counteract herpesvirus infection after in vitro treatment of NK cells with CpGODN. These NK cells showed an increased expression of the inhibitory receptor KIR2DL2 and its ligand HLA-C1, responsible for the reduced NK cell activation. On the basis of previous results that reported the role of KIR3DL2 in CpG-ODN binding [Sivori et al., Blood 2010], we evaluate the way of uptake of CpG-ODN in NK cell lines and its effect on KIRs expression and NK activity status. Our data confirm the role of KIR3DL2 in CpG-ODN uptake and we observed, for the first time, the induction od KIR2DL2 that reduced NK citotoxic activity towards HLA-C1+ target cells. We showed that this modulation via KIR3DL2-CpG-ODN was mediated by specific transcription factors and could explain the KIR2DL2+ NK cell unresponsivness to viral infection after CpG-ODN treatment.