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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Cell Proliferation
  • Dendritic Cells / virology
  • Disease Models, Animal
  • Erythroblasts / virology
  • Female
  • Interferon Type I / metabolism
  • Lectins / pharmacology*
  • Lymph Nodes / virology
  • Macrophages / drug effects
  • Macrophages / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Protective Agents / pharmacology*
  • Retroviridae / drug effects*
  • Retroviridae / pathogenicity*
  • Retroviridae Infections / drug therapy*
  • Sialic Acid Binding Ig-like Lectin 1 / pharmacology*
  • Spleen
  • T-Lymphocytes, Cytotoxic
  • Viral Load


  • Interferon Type I
  • Lectins
  • Protective Agents
  • Sialic Acid Binding Ig-like Lectin 1