Figure 2.
More examples of roles of sialic acids in immunity. Sialic acids are shown as pink diamonds. See key in Figure 1, and the text for details. (A) Siglec-1 (sialoadhesin) expressed on macrophages recognizes Sias in patterns commonly found on microbial pathogens and facilitates phagocytosis. Siglec-1 may also mediate immune cell interactions with one another. Some viruses exploit Siglec-1 binding to gain access to host cells. (B) Certain bacteriophages use Sias on their microbial hosts as “receptors” for invasion. (C) Polysialic acid on immune molecules such as neuropilin on dendritic cells modulates interactions with T cells. (D) Sia-rich secretions on host epithelia can act as decoys for Sia-binding microbes. (E) Sia-covered erythrocytes and Sia-rich plasma proteins can act as “viral traps.” (F) Sias act as biological masks by blocking interactions between intrinsic receptors and underlying glycan structures. (G) Sias on potentially antigenic glycoconjugates prevent the formation of antibodies to “cryptoantigens.” Less commonly, Sias can be autoantigens. (H) Non-self Sias can be metabolically incorporated from dietary sources and become “xeno-autoantigens,” targeted by intrinsic anti-Sia antibodies. (I) Female genital tract reactions to non-self Sia on sperm can lead to reproductive incompatibility. (J) Some mammals, such as cats, have blood groups defined by Sia-containing glycolipids. (K) O-acetylation of Sias can block Sia recognition by intrinsic lectins like Siglecs, and modulate microbial lectin interactions, in a positive or negative fashion. (L) Alpha-2–6 sialylation of IgG-Fc region N-glycans can change the effects of IgG antibodies from activating to inhibitory.