CORRESPONDENCE

Microbial pathogens have evolved many inge-nious ways to evade host innate immune re-sponses and phagocytic clearance (Flannagan et al., 2009; Diacovich and Gorvel, 2010; Neish and Naumann, 2011). Because all microbial and host cell surfaces are decorated with carbohy-drate structures, glycan–receptor interactions play crucial roles in microbial pattern recogni-tion as well as in the regulatory signals that gov-ern normal immune cell activities (Comstock and Kasper, 2006). Consequently, a key viru-lence strategy of many leading pathogens is to display sugars in a fashion that mimics or inter-feres with host glycan–based immune functions (Nizet and Esko, 2009). Sialic acids are 9-carbon-backbone sugars found in abundance on terminal glycan structures of mammalian cell surfaces, including all human cells. Human leukocytes express various mem-bers of a rapidly evolving receptor family known as CD33-related sialic acid–binding immuno-globulin-like lectins (Siglecs); sialylated glycans bind to Siglecs and modulate their function. Because many CD33-related Siglecs have an im-munoreceptor tyrosine-based inhibitory motif (ITIM) and/or ITIM-like motifs in their intra-cellular domain, engagement of sialic acid– containing glycans can mediate an inhibitory signal (Crocker et al., 2007). Consequently