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

PLoS Pathogens

Heike Schmitt¹  Lars Nitschke¹  Marc Lindenberg²  Maxine Swallow²  Catharina Arnold-Schrauf²  Christopher van Helt²  Melanie Gohmert²  Franz Puttur²  Christian Thomas Mayer²  Gulhas Solmaz²  Tim Sparwasser²  Roland Lang³  Martin Messerle⁴  Katharina Lahl⁵  Bart N. Lambrecht⁶ 

[1] Division of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany;Institute for Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research: A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany;Institute of Microbiology, Immunology and Hygiene, University of Erlangen, Erlangen, Germany;Institute of Virology, Medical School Hannover (MHH), Hannover, Germany;Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America;Laboratory of Immunoregulation and Mucosal Immunology, Department of Molecular Biomedical Research, VIB, Ghent, Belgium

关键词: Mouse models;    Spleen;    T cells;    Cytotoxic T cells;    NK cells;    Cell staining;    Cytokines;    Dendritic cells;   

DOI  :  10.1371/journal.ppat.1003648

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY