C-Type Lectin-HIV Attachment on Dendritic Cells Innate Immune Recognition and Processing or Mediators of HIV Transmission?

• Published in: Trends in Glycoscience and Glycotechnology Vol. 14; no. 79; pp. 255 - 271
• Main Authors: Turville, Stuart G, Cameron, Paul U, Hart, Derek, Cunningham, Anthony L
• Format: Journal Article
• Language: English
• Published: FCCA(Forum: Carbohydrates Coming of Age) 2002
• Subjects: CD4; DC-SIGN; HIV gp120; langerin; mannose receptor
• ISSN: 0915-7352; 1883-2113
• DOI: 10.4052/tigg.14.255

Dendritic cells (DC) provide a bridge between the innate and acquired immune system. HIV exploits the complex pathways of microbial antigen uptake and transport by these cells for initial entry and dissemination. Within DCs, some HIV escapes endolysosomal degradation and antigen presentation pathway to be transferred to CD4+ lymphocytes during activation of T cell-mediated immunity. In skin DC the C type lectin receptors (CLRs), langerin on Langerhans cells (LC), and DC-SIGN and mannose receptor (MR) on dermal DC subsets are all capable of binding HIV gp120 through its mannose saccharides. Among DCs only the immature DCs in the periphery can bind HIV through CLRs and this enhances HIV fusion with the target cell membrane via CD4/chemokine receptors, or mediates entry into the endolysosomal pathway. Although CLR transfected cell lines and CLR expressing monocyte derived DC (MoDC) can transfer HIV independent of fusion in vitro, observations of DC ex vivo or in vivo show that CLR-enhanced CD4/CCR5-mediated viral fusion appears to be necessary for viral transfer to T cells. Thus HIV utilizes recognition of abundant high mannose glycans on its envelope protein, for binding to CLRs on skin and mucosal DCs, entry via CD4/CCR5 and transport by DCs to CD4+ lymphocytes in lymph nodes, the major site of viral replication.