%0 Journal Article
%T Absence of Siglec-H in MCMV Infection Elevates Interferon Alpha Production but Does Not Enhance Viral Clearance
%A Franz Puttur equal contributor
%A Catharina Arnold-Schrauf equal contributor
%A Katharina Lahl
%A Gulhas Solmaz
%A Marc Lindenberg
%A Christian Thomas Mayer
%A Melanie Gohmert
%A Maxine Swallow
%A Christopher van Helt
%A Heike Schmitt
%A Lars Nitschke
%A Bart N. Lambrecht
%A Roland Lang
%A Martin Messerle
%A Tim Sparwasser
%J PLOS Pathogens
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1003648
%X Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon ¦Á (IFN¦Á), 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 IFN¦Á levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFN¦Á 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.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003648