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

Uchil, Pradeep D. and Pi, Ruoxi and Haugh, Kelsey A. and Ladinsky, Mark S. and Ventura, John D. and Barrett, Brad S. and Santiago, Mario L. and Bjorkman, Pamela J. and Kassiotis, George and Sewald, Xaver and Mothes, Walther (2019) A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus. Cell Host and Microbe, 25 (1). pp. 87-100. ISSN 1931-3128. PMCID PMC6331384. http://resolver.caltech.edu/CaltechAUTHORS:20190102-092233964

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.chom.2018.11.011DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331384PubMed CentralArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Received 10 June 2018, Revised 8 October 2018, Accepted 5 November 2018, Available online 27 December 2018. This work was supported by NIH grants R01 CA098727 to W.M. and P50GM082545 to W.M. and P.B.J.; the Flow Cytometry Shared Resource of the Yale Cancer CenterP30 CA016359, Yale Center for Cellular and Molecular ImagingS10 OD020142, R21 AI112418 to M.L.S.; funding from the Francis Crick Institute (FC001099) to G.K.; and a fellowship from the China Scholarship Council – Yale World Scholars to R.P. We thank Stephanie Eisenbarth for providing Batf3^(−/−) mice, and Frank Malik, Leonard Evans, and Kim Hasenkrug for suggestions and providing reagents. Author Contributions: P.D.U. and R.P. contributed equally to executing experiments, data analysis, and figure generation. P.D.U., R.P., and W.M. shared the conceptualization, experimental design, interpretation, and manuscript preparation. K.A.H. generated constructs and mouse strains. M.S.L. carried out electron tomography. J.D.V. helped with cryo-sectioning of tissues. B.S.B., M.L.S., and G.K. provided all the reagents, protocols, and EF4.1 mouse strains for carrying out FVC work. M.L.S., X.S., P.J.B., and G.K. contributed to interpretation and discussion of the work. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
NIHR01 CA098727
NIHP50 GM082545
NIHP30 CA016359
NIHS10 OD020142
NIHR21 AI112418
Francis Crick InstituteFC001099
China Scholarship CouncilUNSPECIFIED
Subject Keywords:CD169/Siglec-1; sentinel macrophages; retrovirus; pathogenesis; dissemination; Friend virus; erythroblasts; cDC1
PubMed Central ID:PMC6331384
Record Number:CaltechAUTHORS:20190102-092233964
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190102-092233964
Official Citation: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, A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus, Cell Host & Microbe, Volume 25, Issue 1, 2019, Pages 87-100.e10, ISSN 1931-3128, https://doi.org/10.1016/j.chom.2018.11.011. (http://www.sciencedirect.com/science/article/pii/S1931312818305936)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:91977
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:02 Jan 2019 19:23
Last Modified:24 Jan 2019 15:51

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