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Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent control of cytomegalovirus infection


Lenac Roviš, Tihana; Kučan Brlić, Paola; Kaynan, N.; Juranić Lisnić, Vanda; Brizić, Ilija; Jordan, S.; Tomić, Adriana; Kveštak, Daria; Babić, Marina; Tsukerman, P. et al.
Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent control of cytomegalovirus infection // Journal of experimental nanoscience, 213 (2016), 9; 1835-1850 doi:10.1084/jem.20151899 (međunarodna recenzija, članak, znanstveni)


Naslov
Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent control of cytomegalovirus infection

Autori
Lenac Roviš, Tihana ; Kučan Brlić, Paola ; Kaynan, N. ; Juranić Lisnić, Vanda ; Brizić, Ilija ; Jordan, S. ; Tomić, Adriana ; Kveštak, Daria ; Babić, Marina ; Tsukerman, P. ; Colonna, M. ; Koszinowski, U. ; Messerle, M. ; Mandelboim, O. ; Krmpotić, Astrid ; Jonjić, Stipan

Izvornik
Journal of experimental nanoscience (1745-8080) 213 (2016), 9; 1835-1850

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
MCMV ; evasion ; immune control ; DNAM-1 ; PVR ; NK cell ; monocyte

Sažetak
The poliovirus receptor (PVR) is a ubiquitously expressed glycoprotein involved in cellular adhesion and immune response. It engages the activating receptor DNAX accessory molecule (DNAM)-1, the inhibitory receptor TIGIT, and the CD96 receptor with both activating and inhibitory functions. Human cytomegalovirus (HCMV) down-regulates PVR expression, but the significance of this viral function in vivo remains unknown. Here, we demonstrate that mouse CMV (MCMV) also down-regulates the surface PVR. The m20.1 protein of MCMV retains PVR in the endoplasmic reticulum and promotes its degradation. A MCMV mutant lacking the PVR inhibitor was attenuated in normal mice but not in mice lacking DNAM-1. This attenuation was partially reversed by NK cell depletion, whereas the simultaneous depletion of mononuclear phagocytes abolished the virus control. This effect was associated with the increased expression of DNAM-1, whereas TIGIT and CD96 were absent on these cells. An increased level of proinflammatory cytokines in sera of mice infected with the virus lacking the m20.1 and an increased production of iNOS by inflammatory monocytes was observed. Blocking of CCL2 or the inhibition of iNOS significantly increased titer of the virus lacking m20.1. In this study, we have demonstrated that inflammatory monocytes, together with NK cells, are essential in the early control of CMV through the DNAM-1–PVR pathway

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
062-0621261-1263 - Molekularni mehanizmi citomegalovirusnog izmicanja imunološkom nadzoru (Stipan Jonjić, )
062-0621261-1268 - Uloga imunosubverzivnih citomegalovirusnih gena u latenciji (Astrid Krmpotić, )

Ustanove
Medicinski fakultet, Rijeka

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus


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