engleski

The role of NCR1 receptor in MCMV infection

The NKp46/NCR1 is a type I transmembrane receptor belonging to a family of activating NK cell receptors. Although it is considered one of the most important NK cell-activating receptors for the recognition of infected cells, cellular ligand(s) recognized by this receptor are still mostly unknown. The NCR1 ligands reported so far include influenza virus hemagglutinin and Sendai virus hemmaglutinin/neurominidase. Furthermore, different murine lymphoma and myeloma cell lines were found to express NCR1 ligands. Studies using NCR1-deficient mice revealed increased susceptibility to lethal influenza infection and abberant tumor immunosurveillance. Several groups also reported the expression of NKp46 ligands on dendritic cells and machrophages, emphasizing at the same time the importance of these receptor-ligand interactions in overcoming the viral immune evasion strategies. Our study investigates the in vitro and in vivo role of NCR1 during murine cytomegalovirus (MCMV) infection. The preliminary in vitro results have shown that the infection of B12 cells (SV40 transformed Balb/c MEF) with MCMV resulted in downregulation of an unknown NCR1 ligand. To explore the in vivo role of NCR1 in MCMV infection, we studied the susceptibility of Ncr1 KO (NCR1gfp/gfp) or heterozygous (NCR1+/gfp) mice to infection. Initially, we addressed the early days of infection where NK cells play the dominant role. The results of virus titer measured in different organs 4 days p.i. showed no difference between NCR1+/gfp and NCR1gfp/gfp mice suggesting either lack of involvement of this receptor in MCMV infection or the possibility that viral immunoevasion prevented the NK cell activation via this receptor in the early days of infection. To further explore the possible role of NCR1 in MCMV infection, we focused our attention on the later time points. Surprisingly, virus titer measured in lungs 14 days p.i. revealed impaired control of the virus in NCR1 KO mice. It seems that this phenomenon is NK/CD4+T cells-dependent since depletion of NK- and/or CD4+ T-cells results in annulment of the titer difference. Future plans include further elucidation of physiological role of this major NK cell receptor in innate responses to MCMV through revealing the cross-talk mechanisms of the mentioned lymphocyte subsets, which subsequently result in a better virus control during MCMV infection.

NK cell receptor; MCMV infection

nije evidentirano