EBI3 regulates the NK cell response to mouse cytomegalovirus infection.
Proc Natl Acad Sci U S A
; 114(7): 1625-1630, 2017 02 14.
Article
em En
| MEDLINE
| ID: mdl-28143936
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.
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MEDLINE
Assunto principal:
Células Matadoras Naturais
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Antígenos de Histocompatibilidade Menor
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Receptores de Citocinas
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Muromegalovirus
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Infecções por Citomegalovirus
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article