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Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1625-1630. doi: 10.1073/pnas.1700231114. Epub 2017 Jan 31.

EBI3 regulates the NK cell response to mouse cytomegalovirus infection.

Author information

1
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.
2
Department of Microbiology and Immunology, Stanford University, Palo Alto, CA 94304.
3
Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby DK-2800, Denmark.
4
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; lewis.lanier@ucsf.edu.
5
Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143.

Abstract

Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 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 IFNγ 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 wild-type (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.

KEYWORDS:

EBI3; cytomegalovirus; natural killer cell

PMID:
28143936
PMCID:
PMC5321027
DOI:
10.1073/pnas.1700231114
[Indexed for MEDLINE]
Free PMC Article

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