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Cell Host Microbe. 2019 Jan 9;25(1):87-100.e10. doi: 10.1016/j.chom.2018.11.011. Epub 2018 Dec 27.

A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus.

Author information

1
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: pradeep.uchil@yale.edu.
2
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
3
Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
4
Division of Infectious Diseases, University of Colorado Denver, 12700 East 19th Avenue, Aurora, CO 80045, USA.
5
Retrovirus Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
6
Max von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
7
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: walther.mothes@yale.edu.

Abstract

Lymph- and blood-borne retroviruses exploit CD169/Siglec-1-mediated capture by subcapsular sinus and marginal zone metallophilic macrophages for trans-infection of permissive lymphocytes. However, the impact of CD169-mediated virus capture on retrovirus dissemination and pathogenesis in vivo is unknown. In a murine model of the splenomegaly-inducing retrovirus Friend virus complex (FVC) infection, we find that while CD169 promoted draining lymph node infection, it limited systemic spread to the spleen. At the spleen, CD169-expressing macrophages captured incoming blood-borne retroviruses and limited their spread to the erythroblasts in the red pulp where FVC manifests its pathogenesis. CD169-mediated retroviral capture activated conventional dendritic cells 1 (cDC1s) and promoted cytotoxic CD8+ T cell responses, resulting in efficient clearing of FVC-infected cells. Accordingly, CD169 blockade led to higher viral loads and accelerated death in susceptible mouse strains. Thus, CD169 plays a protective role during FVC pathogenesis by reducing viral dissemination to erythroblasts and eliciting an effective cytotoxic T lymphocyte response via cDC1s.

KEYWORDS:

CD169/Siglec-1; Friend virus; cDC1; dissemination; erythroblasts; pathogenesis; retrovirus; sentinel macrophages

PMID:
30595553
PMCID:
PMC6331384
DOI:
10.1016/j.chom.2018.11.011
[Indexed for MEDLINE]
Free PMC Article

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