Journal article
EBI3 regulates the NK cell response to mouse cytomegalovirus infection
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.
Language: | English |
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Publisher: | National Academy of Sciences |
Year: | 2017 |
Pages: | 1625-1630 |
ISSN: | 10916490 and 00278424 |
Types: | Journal article |
DOI: | 10.1073/pnas.1700231114 |
ORCIDs: | Folkersen, Lasse Westergaard |
Animals Cell Line Cells, Cultured Cytomegalovirus Infections Ebi3 protein, mouse Gene Expression Host-Pathogen Interactions Humans Interleukin-12 Interleukin-18 Killer Cells, Natural Mice, Inbred C57BL Mice, Knockout Minor Histocompatibility Antigens Muromegalovirus Receptors, Cytokine