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 re... More
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.
