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Metabolic sialic acid blockade lowers the activation threshold of moDCs for TLR stimulation
Author(s) -
Büll Christian,
ColladoCamps Estel,
KersRebel Esther D,
Heise Torben,
Søndergaard Jonas N,
Brok Martijn H,
Schulte Barbara M,
Boltje Thomas J,
Adema Gosse J
Publication year - 2017
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2016.105
Subject(s) - sialic acid , receptor , chemistry , stimulation , siglec , t cell , biochemistry , immune system , microbiology and biotechnology , biology , immunology , endocrinology
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 5 3F ax 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 5 3F ax 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 5 3F ax 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 5 3F ax Neu5Ac could therefore potentially be used to generate more potent DC‐based vaccines for induction of robust anti‐viral or anti‐tumor immune responses.