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

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. © 2013 puttur et al.