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1.
PLoS Pathog ; 9(9): e1003648, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24086137

RESUMEN

Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon α (IFNα), a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV) infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC)-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H⁺ pDCs is terminally labeled with red fluorescent protein (RFP). Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNα levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNα production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies.


Asunto(s)
Células Dendríticas/inmunología , Infecciones por Herpesviridae/inmunología , Interferón-alfa/inmunología , Lectinas/inmunología , Modelos Inmunológicos , Muromegalovirus/fisiología , Células Plasmáticas/inmunología , Receptores de Superficie Celular/inmunología , Animales , Células Dendríticas/metabolismo , Células Dendríticas/patología , Infecciones por Herpesviridae/genética , Infecciones por Herpesviridae/metabolismo , Infecciones por Herpesviridae/patología , Interferón-alfa/genética , Interferón-alfa/metabolismo , Lectinas/genética , Lectinas/metabolismo , Ratones , Ratones Noqueados , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Replicación Viral/genética , Replicación Viral/inmunología
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