期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 7, 页码 1625-1630出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1700231114
关键词
natural killer cell; EBI3; cytomegalovirus
资金
- National Institutes of Health [AI066897, AI068129]
- Parker Institute for Cancer Immunotherapy
- Lundbeck Foundation Postdoctoral Fellowship
- NIH [U19AI057229, U19AI100627, R33CA183654, R33CA0183692, R01GM10983601, R01CA184968, R01CA19665701, R21CA183660, R01NS08953301, 5UH2AR067676, R01HL120724]
- Northrop-Grumman Corporation
- Novartis [CMEK162AUS06T]
- Pfizer [123214]
- Juno Therapeutics [122401]
- Department of Defense [OC110674, W81XWH-14-1-0 180]
- Gates Foundation [OPP1113682]
- Food and Drug Administration [BAA-15-00121]
Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virusinduced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection. The induction of EBI3 protein expression in mouse NK cells is a late activation event. Thus, early activation events of NK cells, such as IFN. production and CD69 expression, were not affected in EBI3-deficient (Ebi3(-/-)) C57BL/6 (B6) mice during MCMV infection. Furthermore, comparable levels of early viral replication in spleen and liver were observed in MCMV-infected Ebi3(-/-) and wildtype (WT) B6 mice. Interestingly, the viral load in salivary glands and oral lavage was strongly decreased in the MCMV-infected Ebi3(-/-)B6 mice, suggesting that EBI3 plays a role in the establishment of MCMV latency. We detected a decrease in the sustained IL-10 production by NK cells and lower serum levels of IL-10 in the MCMV-infected Ebi3(-/-)B6 mice. Furthermore, we observed an increase in dendritic cell maturation markers and an increase in activated CD8(+) T cells. Thus, EBI3 dampens the immune response against MCMV infection, resulting in prolonged viral persistence.
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