Absence of Siglec-H in MCMV Infection Elevates Interferon Alpha Production but Does Not Enhance Viral Clearance: e1003648

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 viv...

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Bibliographic Details
Published in:PLoS pathogens 2013-09, Vol.9 (9)
Main Authors: Puttur, Franz, Arnold-Schrauf, Catharina, Lahl, Katharina, Solmaz, Gulhas, Lindenberg, Marc, Mayer, Christian Thomas, Gohmert, Melanie, Swallow, Maxine, Helt, Christopher van, Schmitt, Heike, Nitschke, Lars, Lambrecht, Bart N, Lang, Roland, Messerle, Martin, Sparwasser, Tim
Format: Article
Language:English
Subjects:
Artificial chromosomes
Cytomegalovirus
Experiments
Immunology
Ligands
Murine cytomegalovirus
Viral infections
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Summary: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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1003648