Naslov
Mouse cytomegalovirus restores host 'self' to prevent 'missing self'

Autori
Babić Čač, M ; Zafirova, B ; Mitrović, M ; Tršan, T ; Pyzik, M ; Krmpotić, A ; Vidal, S ; Jonjić S.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Godišnji sastanak Hrvatskog imunološkog društva 2011 / - , 2011

Skup
Godišnji sastanak Hrvatskog imunološkog društva 2011

Mjesto i datum
Rabac, Hrvatska, 07.10.2011. - 09.10.2011

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
MCMV; NK cells; Ly49 receptors; missing self

Sažetak
Regulation of the NK cell response in acute mouse cytomegalovirus (MCMV) infection is dependent on the fine balance of signals coming from activating and inhibitory receptors expressed on their cell surface. Here, we provide evidence that MCMV protein, m04/gp34, is essential for the recognition of infected cells by several activating Ly49 receptors, which recognize MHC I molecule, together with m04 product and another, so far unidentified viral component. Our results show that the recognition of MHC I/m04 complex by Ly49L+ NK cells in BALB.K mice leads to a specific expansion of this NK cell subset and their dominant IFN-γ production resulting in faster clearance of infectious virus from the organ of these mice when compared to BALB/c or BALB.B mice (day 6-10) (Pyzik M et al, J Exp Med, 2011). However, in the early days of infection (day 1-4), mice of H-2d and H-2k haplotype are unable to restrain viral replication in spite of the early and strong downregulation of MHC I molecules from the surface of infected cells which should lead to a 'missing self'-mediated recognition by NK cells. It has been suggested that m04/gp34 might inhibit NK cell activation through its ability to escort MHC I to the cell surface and serve as an NK cell decoy. Our hypothesis was that this mechanism evolved to prevent NK cell activation and killing by restoring the 'self' signature and allowing the engagement of inhibitory Ly49 receptors by their natural ligands. Our results indeed show that the ligation of an inhibitory Ly49A NK cell receptor leads to the protection of infected cells from specific lysis, impaired proliferation of NK cells and loss of control of viral replication in vivo in mice of H-2d and H-2k haplotype, all during the first 3 days of infection (Babić M et al, J Exp Med, 2010). In addition, we here suggest that the strong 'missing self'-mediated control of Δm04 MCMV infection by NK cells does not impair the later ongoing CD8+ T cell response. Our results implicate that this is most likely due to the preserved number and activity of plasmacytoid DCs and maintainance of conventional DCs, when compared to WT MCMV infection.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA