Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / pathology
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Herpesviridae Infections / genetics
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Herpesviridae Infections / immunology*
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Herpesviridae Infections / metabolism
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Herpesviridae Infections / pathology
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Interferon-alpha / genetics
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Interferon-alpha / immunology*
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Interferon-alpha / metabolism
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Lectins / genetics
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Lectins / immunology*
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Lectins / metabolism
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Mice
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Mice, Knockout
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Models, Immunological*
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Muromegalovirus / physiology*
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Plasma Cells / immunology*
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Plasma Cells / metabolism
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Plasma Cells / pathology
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology*
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Receptors, Cell Surface / metabolism
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Virus Replication / genetics
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Virus Replication / immunology
Substances
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Interferon-alpha
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Lectins
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Receptors, Cell Surface
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Siglech protein, mouse
Grants and funding
This study was funded by the Deutsche Forschungsgemeinschaft SFB-587 and SFB-900 (Sonderforschungsbereich 587, 900 (Project number: CRC900 ProjectB7)). MM was supported by SFB-900 (Project number: CRC900 ProjectB1). CAS was supported by the Boehringer Ingelheim Fonds, Foundation for Basic Research in Medicine. CTM was supported by the German National Academic Foundation. The Cell Sorting Core Facility of the Hannover Medical School was supported in part by Braukmann-Wittenberg-Herz-Stiftung and Deutsche Forschungsgemeinschaft. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.