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

作者：Puttur Franz^*; Arnold Schrauf Catharina; Lahl Katharina; Solmaz Gulhas; Lindenberg Marc; Mayer Christian Thomas; Gohmert Melanie; Swallow Maxine; van Helt Christopher; Schmitt Heike; Nitschke Lars; Lambrecht Bart N; Lang Roland; Messerle Martin; Sparwasser Tim

来源：PLoS Pathogens, 2013, 9(9): e1003648.

DOI：10.1371/journal.ppat.1003648

Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon alpha (IFN alpha), 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 %26quot;pDCre%26quot; 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.

• 出版日期2013-9