Shapiro, Michael J

Abstract Sialic acids are the terminal modification on glycoproteins and glycolipids. The sialic acid transferase ST8Sia6 generates a2,8-linked disialic acids on O-linked glycoproteins, which bind to the inhibitory receptor Siglec-E on innate immune cells and suppress immune activation. Recently, our lab has shown that ST8Sia6 expression on tumor cells inhibits the immune response through Siglec-E, leading to increased tumor growth and decreased survival. Therefore, the products of ST8Sia6 can modulate the immune response to tumors. Our lab has generated ST8Sia6 knockout (KO) mice, and we seek to understand the role of ST8Sia6 in regulating the immune response to pathogens. We find that ST8Sia6 KO mice, when challenged with influenza virus, clear the infection significantly faster than wildtype controls, suggesting that absence of ST8Sia6 reduces inhibition of the innate compartment, thereby increasing immune recruitment to infection. This data suggests an important role for interactions between Siglec-E and ST8Sia6-generated disialic acids in immune regulation and recruitment to infection sites.