Projects per year
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 language | English |
---|---|
Pages (from-to) | 7826-7831 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 110 |
Issue number | 19 |
DOIs | |
Publication status | Published - 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
Fingerprint
Dive into the research topics of 'Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation'. Together they form a unique fingerprint.Projects
- 1 Finished
-
Aref#d: 19149. Role of Siglecs in Disease (Senior Research Fellowship)
1/11/07 → 30/04/13
Project: Research