Viral regulation of PVR reveals robust capacity of DNAM-1 in cytomegalovirus control by NK cells and macrophages (CROSBI ID 635459)
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Podaci o odgovornosti
Tihana Lenac Rovis, Paola Kucan, Noa Stanietsky, Vanda Juranic Lisnic, Ilija Brizic, Stefan Jordan, Adriana Tomic, Marina Babic, Pinchas Tsukerman, Marco Colonna, Martin Messerle, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
engleski
Viral regulation of PVR reveals robust capacity of DNAM-1 in cytomegalovirus control by NK cells and macrophages
The poliovirus receptor (PVR, CD155) is a highly conserved and ubiquitously expressed glycoprotein that plays a role in the immune response to tumors and viruses, acting as stress induced ligand. It engages the activating receptor DNAM-1, expressed on the majority of immune cells, the inhibitory receptor TIGIT and CD96, receptor for which both activating and inhibitory functions have been described. We have demonstrated that mouse cytomegalovirus (MCMV) downmodulates surface expression of PVR and characterized the viral protein involved, named m20.1. Since PVR can ligate both inhibitory and activating immune receptors, the consequence of this viral downregulation in vivo was hardly predictable. We showed that MCMV mutant lacking PVR inhibitor was attenuated in normal mice but not in DNAM-1-/- mice, suggesting the dominance of DNAM-1 over other PVR receptors. The attenuation of Δm20.1 MCMV was only partially reversed by NK cell depletion, whereas depletion of macrophages abolished this phenotype. A strong effect of macrophages was associated with their dominant expression of DNAM-1 upon in vivo infection, while TIGIT and CD96 were absent on these cells. We also observed increased production of iNOS in macrophages of mice infected with Δm20.1 virus, as well as increased level of proinflammatory cytokines in sera of those mice, suggesting macrophage polarization towards the inflammation. Altogether, our data show that the deletion of viral inhibitor of PVR augments virus control by NK cells and macrophages via engagement of DNAM-1.
PVR; DNAM-1; MCMV
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Podaci o prilogu
2015.
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
REGULATORY MYELOID CELLS (MRC) IN HEALTH AND DISEASE conference and workshop
poster
14.09.2015-16.09.2015
Kraków, Poljska