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Metabolic sialic acid blockade lowers the activation threshold of moDCs for TLR stimulation.
Metabolic sialic acid blockade lowers the activation threshold of moDCs for TLR stimulation.
- Source :
-
Immunology and cell biology [Immunol Cell Biol] 2017 Apr; Vol. 95 (4), pp. 408-415. Date of Electronic Publication: 2016 Nov 22. - Publication Year :
- 2017
-
Abstract
- Sialic acid sugars cover the surface of dendritic cells (DCs) and have been suggested to impact several aspects of DC biology. Research into the role of sialic acids in DCs, however, is complicated by the limited number of tools available to modulate sialic acid expression. Here we report on a synthetic, fluorinated sialic acid mimetic, Ac <subscript>5</subscript> 3F <subscript>ax</subscript> Neu5Ac, which potently blocks sialic acid expression in human monocyte-derived DCs (moDCs). Sialic acid blockade enhanced the responsiveness of moDCs to Toll-like receptor (TLR) stimulation as measured by increased maturation marker expression and cytokine production. Consequently, the T-cell activation capacity of Ac <subscript>5</subscript> 3F <subscript>ax</subscript> Neu5Ac-treated moDCs was strongly increased. In addition to sialic acids, moDCs also expressed the sialic acid-binding immunoglobulin-like lectins (Siglecs) -3, -5, -7, -9 and -10, immune inhibitory receptors recognizing these sialic acids. Treatment with Ac <subscript>5</subscript> 3F <subscript>ax</subscript> Neu5Ac abrogated putative cis and trans interactions between sialic acids and Siglec-7/-9. Together, these data indicate that sialic acids limit the activation of moDCs via the TLR pathway, potentially by interacting with Siglec-7 or Siglec-9. Metabolic sialic acid blockade with Ac <subscript>5</subscript> 3F <subscript>ax</subscript> Neu5Ac could therefore potentially be used to generate more potent DC-based vaccines for induction of robust anti-viral or anti-tumor immune responses.
- Subjects :
- Antigens, CD metabolism
Antigens, Differentiation metabolism
Antigens, Differentiation, Myelomonocytic metabolism
Biomimetics
Cell Differentiation
Cells, Cultured
Cytokines metabolism
Dendritic Cells drug effects
Humans
Lectins metabolism
Lipopolysaccharides immunology
Lymphocyte Culture Test, Mixed
Monocytes immunology
N-Acetylneuraminic Acid analogs & derivatives
N-Acetylneuraminic Acid antagonists & inhibitors
Poly I-C immunology
Sialic Acid Binding Immunoglobulin-like Lectins metabolism
Toll-Like Receptors metabolism
Dendritic Cells immunology
Lymphocyte Activation drug effects
N-Acetylneuraminic Acid pharmacology
Sialic Acids pharmacology
Signal Transduction drug effects
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1711
- Volume :
- 95
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Immunology and cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 27874015
- Full Text :
- https://doi.org/10.1038/icb.2016.105