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

Uchil, Pradeep D.; Pi, Ruoxi; Haugh, Kelsey A.; Ladinsky, Mark S.; Ventura, John D.; Barrett, Brad S.; Santiago, Mario L.; Bjorkman, Pamela J.; Kassiotis, George; Sewald, Xaver und Mothes, Walther (2019): A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus. In: Cell Host & Microbe, Bd. 25, Nr. 1

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 CDS(+)8 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1931-3128
• Sprache: Englisch