Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation

Norihito Kawasaki, Jose Luis Vela, Corwin M. Nycholat, Christoph Rademacher, Archana Khurana, Nico van Rooijen, Paul R. Crocker, Mitchell Kronenberg, James C. Paulson

    Research output: Contribution to journalArticle

    59 Citations (Scopus)

    Abstract

    Invariant natural killer T (iNKT) cells induce a protective immune response triggered by foreign glycolipid antigens bound to CD1d on antigen-presenting cells (APCs). A limitation of using glycolipid antigens to stimulate immune responses in human patients has been the inability to target them to the most effective APCs. Recent studies have implicated phagocytic CD169+ macrophages as major APCs in lymph nodes for priming iNKT cells in mice immunized with glycolipid antigen in particulate form. CD169 is known as sialoadhesin (Sn), a macrophage-specific adhesion and endocytic receptor of the siglec family that recognizes sialic acid containing glycans as ligands. We have recently developed liposomes decorated with glycan ligands for CD169/Sn suitable for targeted delivery to macrophages via CD169/Sn-mediated endocytosis. Here we show that targeted delivery of a lipid antigen to CD169+ macrophages in vivo results in robust iNKT cell activation in liver and spleen using nanogram amounts of antigen. Activation of iNKT cells is abrogated in Cd169-/- mice and is macrophage-dependent, demonstrating that targeting CD169+ macrophages is sufficient for systemic activation of iNKT cells. When pulsed with targeted liposomes, human monocyte-derived dendritic cells expressing CD169/Sn activated human iNKT cells, demonstrating the conservation of the CD169/Sn endocytic pathway capable of presenting lipid antigens to iNKT cells.

    Original languageEnglish
    Pages (from-to)7826-7831
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume110
    Issue number19
    DOIs
    Publication statusPublished - 7 May 2013

    Keywords

    • IN-VIVO DEPLETION
    • antigen presentation
    • RESPONSES
    • DENDRITIC CELLS
    • antigen delivery
    • NKT CELLS
    • ALPHA-GALACTOSYLCERAMIDE
    • CAMPYLOBACTER-JEJUNI
    • immune modulation
    • CUTTING EDGE
    • EXPRESSION
    • CD169(+) MACROPHAGES
    • SIALOADHESIN

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