Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance.

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.

• Authors: Franz Puttur, Catharina Arnold-Schrauf, Katharina Lahl, Gulhas Solmaz, Marc Lindenberg, Christian Thomas Mayer, Melanie Gohmert, Maxine Swallow, Christopher van Helt, Heike Schmitt, Lars Nitschke, Bart N Lambrecht, Roland Lang, Martin Messerle, Tim Sparwasser
• Journal: PLoS pathogens (PLoS Pathog) Vol. 9 Issue 9 Pg. e1003648 ( 2013) ISSN: 1553-7374 [Electronic] United States
• PMID: 24086137 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-alpha
• Lectins
• Receptors, Cell Surface
• Siglech protein, mouse

Topics

• Animals
• Dendritic Cells (immunology, metabolism, pathology)
• Herpesviridae Infections (genetics, immunology, metabolism, pathology)
• Interferon-alpha (genetics, immunology, metabolism)
• Lectins (genetics, immunology, metabolism)
• Mice
• Mice, Knockout
• Models, Immunological
• Muromegalovirus (physiology)
• Plasma Cells (immunology, metabolism, pathology)
• Receptors, Cell Surface (genetics, immunology, metabolism)
• Virus Replication (genetics, immunology)