engleski

The importance of cytolytic mechanisms in NK-cell response to mouse cytomegalovirus infection

The effective natural killer (NK) cell control of mouse cytomegalovirus (MCMV) infection in C57BL/6 mice depends on binding of the Ly49H NK-cell activation receptor to the m157 MCMV glycoprotein. Here we investigated the contribution of the cytolytic mechanisms in control of MCMV in mice that possess Cmv1 locus which encodes the Ly49H receptor. To that aim we analyzed Ly49H+ mice deficient for perforin (prf-/-), as well as mice deficient for granzyme A and B (gzmAxB-/-). Mice were infected with either wild type MCMV or mutant virus lacking m157 (m157). Both prf-/- and gzmA×B-/- mice showed much higher MCMV titers in organs as compared to control C57BL/6 mice. In prf-/- mice infected with wild type MCMV we observed no differences in viral titers as compared to the group of mice infected with m157. These virus titers were also similar to those in C57BL/6 mice infected with m157. Base on this, we concluded that MCMV control via Ly49H+ NK cells depends on cytolytic mechanisms. Next we investigated secretion of IFN-by NK cells in prf-/- mice after infection with MCMV. Interestingly, we observed higher amount of IFN- in prf-/- mice, as compared to control animals. To evaluate the role of Ly49H in proliferation and maintenance of NK cells we performed Brdu assay at day 4.5 p.i. Surprisingly, in comparison to control mice, prf-/- mice showed much higher number of Brdu+ Ly49H+ NK cells with the phenotype of mature cells. Altogether, these data clearly demonstrated the importance of the cytolytic mechanisms in control of MCMV.

Perforin; MCMV; Ly49H NK cells

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