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

Autor: Stipan Jonjić, Adriana Tomic, Marina Babić, Ilija Brizić, Ulrich H. Koszinowski, Astrid Krmpotić, Ofer Mandelboim, Martin Messerle, Noa S. Kaynan, Stefan Jordan, Vanda Juranić Lisnić, Marco Colonna, Paola Kucan Brlic, Daria Kveštak, Tihana Lenac Rovis, Pinchas Tsukerman
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Antigens
Differentiation
T-Lymphocyte
0301 basic medicine
DOWN-REGULATION
CD96
DNAM-1 CD226
Immunology
Nitric Oxide Synthase Type II
MACROPHAGE ACTIVATION
CCL2
DENDRITIC CELLS
Article
Monocytes
Proinflammatory cytokine
Mice
03 medical and health sciences
NATURAL-KILLER-CELLS
TIGIT
MCMV
evasion
immune control
DNAM-1
PVR
NK cell
monocyte
Animals
Immunology and Allergy
CD155
Receptor
Research Articles
GENE-EXPRESSION
Mice
Inbred BALB C
MURINE CYTOMEGALOVIRUS
biology
BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences
virus diseases
dNaM
Interleukin-12
eye diseases
3. Good health
Cell biology
Killer Cells
Natural
Mice
Inbred C57BL
030104 developmental biology
Cytomegalovirus Infections
biology.protein
Receptors
Virus
VIRUS
sense organs
BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti
Poliovirus Receptor
RESPONSES
Zdroj: JOURNAL OF EXPERIMENTAL MEDICINE
Volume 213
Issue 9
The Journal of Experimental Medicine
ISSN: 1540-9538
Popis: Jonjic et al. show that inflammatory macrophages play an essential role in the control of murine CMV (MCMV) infection through a DNAM-1–PVR pathway.
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.
Databáze: OpenAIRE
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