Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon a (IFNa), a critical antiviral 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 IFNa levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNa
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.