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A protective role for the lectin CD169/Siglec-1 against a pathogenic murine retrovirus
journal contributionposted on 2019-12-19, 18:06 authored by Pradeep D Uchil, Ruoxi Pi, Kelsey A Haugh, Mark S Ladinsky, John D Ventura, Brad S Barrett, Mario L Santiago, Pamela J Bjorkman, George Kassiotis, Xaver Sewald, Walther Mothes
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.
Crick (Grant ID: 10099, Grant title: Kassiotis FC001099)
CD169/Siglec-1Friend viruscDC1disseminationerythroblastspathogenesisretrovirussentinel macrophagesAnimalsCD8-Positive T-LymphocytesCell ProliferationDendritic CellsDisease Models, AnimalErythroblastsFemaleInterferon Type ILectinsLymph NodesMacrophagesMaleMiceMice, Inbred BALB CMice, Inbred C57BLProtective AgentsRetroviridaeRetroviridae InfectionsSialic Acid Binding Ig-like Lectin 1SpleenT-Lymphocytes, CytotoxicViral LoadKassiotis FC001099Immunology0605 Microbiology1108 Medical Microbiology