Metabolic sialic acid blockade lowers the activation threshold of moDCs for TLR stimulation

Autor: Torben Heise, Barbara M. Schulte, Thomas J. Boltje, Estel Collado-Camps, Gosse J. Adema, Esther D. Kers-Rebel, Jonas Nørskov Søndergaard, Martijn H. den Brok, Christian Büll
Rok vydání: 2017
Předmět:
Lipopolysaccharides
0301 basic medicine
T-Lymphocytes
Cellular differentiation
medicine.medical_treatment
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Immunology
Antigens
Differentiation
Myelomonocytic
Stimulation
Synthetic Organic Chemistry
Biology
Lymphocyte Activation
Monocytes
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
Antigen
Antigens
CD
Biomimetics
Immunity
Lectins
medicine
Humans
Immunology and Allergy
Receptor
Cells
Cultured
Sialic Acid Binding Immunoglobulin-like Lectins
Toll-Like Receptors
Cell Differentiation
Dendritic Cells
Cell Biology
Antigens
Differentiation
N-Acetylneuraminic Acid
Sialic acid
carbohydrates (lipids)
Poly I-C
030104 developmental biology
Cytokine
Biochemistry
chemistry
Sialic Acids
Cytokines
Lymphocyte Culture Test
Mixed
Signal Transduction
030215 immunology
Zdroj: Immunology and Cell Biology, 95, 4, pp. 408-415
Immunology and Cell Biology, 95, 408-415
ISSN: 0818-9641
Popis: Contains fulltext : 177820.pdf (Publisher’s version ) (Closed access) 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, Ac53FaxNeu5Ac, 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 Ac53FaxNeu5Ac-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 Ac53FaxNeu5Ac 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 Ac53FaxNeu5Ac could therefore potentially be used to generate more potent DC-based vaccines for induction of robust anti-viral or anti-tumor immune responses.
Databáze: OpenAIRE
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