PLoS Pathogens | |
Absence of Siglec-H in MCMV Infection Elevates Interferon Alpha Production but Does Not Enhance Viral Clearance | |
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
【 预 览 】
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