SIGN-R1 contributes to protection against lethal pneumococcal infection in mice.

Rapid clearance of pathogens is essential for successful control of pyogenic bacterial infection. Previous experiments have shown that antibody to specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1 inhibits uptake of capsular polysaccharide by marginal zone macrophages, suggesting a role for SIGN-R1 in this process. We now demonstrate that mice lacking SIGN-R1 (a mouse homologue of human dendritic cell-SIGN receptor) are significantly more susceptible to Streptococcus pneumoniae infection and fail to clear S. pneumoniae from the circulation. Marginal zone and peritoneal macrophages show impaired bacterial recognition associated with an inability to bind T-independent type 2 antigens such as dextran. Our work represents the first evidence for a protective in vivo role for a SIGN family molecule.

Interaction of CD22 with alpha2,6-linked sialoglycoconjugates: innate recognition of self to dampen B cell autoreactivity?

CD22 is a glycoprotein that associates with the B cell antigen receptor and acts as a negative regulator of receptor signaling; its extracellular domain binds alpha2,6-linked sialoglycoconjugates. Here we show that B cell activation by antigen displayed on the surface of a target cell is depressed if the target co-expresses alpha2,6-sialoglycoconjugates: this inhibition is dependent on CD22. Since sialylation is largely a feature of higher eukaryotes with alpha2,6-sialyltransferase increasing during inflammation, we propose that the CD22 / sialoglycoconjugate interaction allows context-dependent B cell activation, possibly acting as a crude discriminator of self in order to dampen B cell autoreactivity and the initiation of autoimmunity.