Glycobiology of Innate Immunology by Cheorl-Ho Kim

Author:Cheorl-Ho Kim
Language: eng
Format: epub
ISBN: 9789811690815
Publisher: Springer Singapore

7.7.3 SA-Recognition Tropism of Siglecs

SAs on immune cells can be defined as biological masking agents and cell pattern-recognizing agents. SA-containing carbohydrates present on DCs are recognized by Siglec receptor-holding effector cells. Although there are many SA species in vertebrates, and they have good interactions with Siglecs [136] (Table 7.2), two common SA glycans recognized as ligands by Siglecs are shown (Fig. 7.8a, b). For example, high α2,6-SA contents of tolerogenic DCs and immature DCs are recognized by inhibiting Siglecs produced by effector T cells and this is indeed a host tolerance-induced mechanism. The enhanced binding capacities of Siglec-1, Siglec-2, and Siglec-7 are correlated with the high SA levels of mature DCs. DCs also express themselves as Siglecs on their surfaces. For biological masking functions, SAs shield the host cells from pathogenic binding and thus consequently prevent autoimmune responses. Therefore, the concentration of SAs expressed on human cell surfaces is relatively increased. High SA contents are caused as a result of acute-phase responses. SAs also upregulate immune cell activities and discriminate the “self-” antigens from the “nonself” ones. The majority of DC Siglecs bind in the cis-type. However, sialidases can inhibit Siglec–SA binding through the extrinsic or intrinsic action of sialidases. More specifically, sialidases can improve phagocytosis operated by human monocyte-derived DCs (mo-DCs) and mature mo-DCs. Sialidase treatment increases the immune response of MDDCs [137]. E. coli phagocytosis is also improved by SA moieties. Sialidase treatment improves the capacity of mo-DCs to phagocytose pathogenic E. coli isolates, as removal of SAs from the surfaces of mo-DCs highly sialylates induced mo-DC maturation and decreased micropinocytosis [138]. ST6Gal-1-null BMDCs have a higher phagocytic activity compared to that of normal cell types [23]. Desialylated MDDCs increase the phagocytic capacity of E. coli. Treatment of MDDCs with sialidase increases the level of NF-κB activation and cytokine gene expression, consequently increasing the phagocytic capacity of the cells, indicating that desialylated mo-DCs enhance immunological functions including cytokine gene expression and NF-κB activation, as well as IFN-γ gene production by T cells. E. coli phagocytic capacity is influenced by the SA species. BMDCs isolated from ST6Gal-1 KO mice increase the phagocytic activity against E. coli. Neuraminidase influences the reorganization of the cytoskeleton and activates Rho-GTPases. Phagocytosis remodels the actin cytoskeleton and activates Rho small-type GTPases [137].Table 7.2Human Siglec family and binding of sialic acids to SA-recognition molecules. Words in red indicate CD33-related Siglecs. , Sialic acid (SA); , galactose (Gal); , N-acetylglucosamine (GlcNAc); , N-acetylgalactosamine (GalNAc); , fucose (Fuc)

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