Interferon-Inducible Mechanism of Dendritic Cell-Mediated HIV-1 Dissemination Is Dependent on Siglec-1/CD169

PLoS Pathogens

Xinwei Yu¹  Björn M. Reinhard¹  Suryaram Gummuluru²  Wendy Blay Puryear²  Nora P. Ramirez²  Suzanne D. Geer²  Hisashi Akiyama² 

[1] Department of Chemistry and the Photonics Center, Boston University, Boston, Massachusetts, United States of America;Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America

关键词: HIV-1;    T cells;    HIV;    Antibodies;    Monocytes;    Cell differentiation;    Immunoprecipitation;    Sialic acids;   

DOI  :  10.1371/journal.ppat.1003291

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Human immunodeficiency virus type 1 (HIV-1) interactions with myeloid dendritic cells (DCs) can result in virus dissemination to CD4+ T cells via a trans infection pathway dependent on virion incorporation of the host cell derived glycosphingolipid (GSL), GM3. The mechanism of DC-mediated trans infection is extremely efficacious and can result in infection of multiple CD4+ T cells as these cells make exploratory contacts on the DC surface. While it has long been appreciated that activation of DCs with ligands that induce type I IFN signaling pathway dramatically enhances DC-mediated T cell trans infection, the mechanism by which this occurs has remained unclear until now. Here, we demonstrate that the type I IFN-inducible Siglec-1, CD169, is the DC receptor that captures HIV in a GM3-dependent manner. Selective downregulation of CD169 expression, neutralizing CD169 function, or depletion of GSLs from virions, abrogated DC-mediated HIV-1 capture and trans infection, while exogenous expression of CD169 in receptor-naïve cells rescued GSL-dependent capture and trans infection. HIV-1 particles co-localized with CD169 on DC surface immediately following capture and subsequently within non-lysosomal compartments that redistributed to the DC – T cell infectious synapses upon initiation of T cell contact. Together, these findings describe a novel mechanism of pathogen parasitization of host encoded cellular recognition machinery (GM3 – CD169 interaction) for DC-dependent HIV dissemination.

【 授权许可】

CC BY