Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands.
J Exp Med
; 204(5): 1217-25, 2007 May 14.
Article
en En
| MEDLINE
| ID: mdl-17485516
ABSTRACT
The salivary glands represent a major site of cytomegalovirus replication and transmission to other hosts. Despite control of viral infection by strong T cell responses in visceral organs cytomegalovirus replication continues in the salivary glands of mice, suggesting that the virus exploits the mucosal microenvironment. Here, we show that T cell immunity in the salivary glands is limited by the induction of CD4 T cells expressing the regulatory cytokine interleukin (IL)-10. Blockade of IL-10 receptor (IL-10R) with an antagonist antibody dramatically reduced viral load in the salivary glands, but not in the spleen. The mucosa-specific protection afforded by IL-10R blockade was associated with an increased accumulation of CD4 T cells expressing interferon gamma, suggesting that IL-10R signaling limits effector T cell differentiation. Consistent with this, an agonist antibody targeting the tumor necrosis factor receptor superfamily member OX40 (TNFRSF4) enhanced effector T cell differentiation and increased the number of interferon gamma-producing T cells, thus limiting virus replication in the salivary glands. Collectively, the results indicate that modulating effector T cell differentiation can counteract pathogen exploitation of the mucosa, thus limiting persistent virus replication and transmission.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Glándulas Salivales
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Replicación Viral
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Linfocitos T CD4-Positivos
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Diferenciación Celular
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Interleucina-10
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Muromegalovirus
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Infecciones por Herpesviridae
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos