title: Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake.
abstract: Sialic acid-binding immunoglobulin-like lectins (siglecs) are expressed predominantly in the haemopoietic and immune systems and exhibit specificities for both the linkage and the nature of sialic acids in N-glycans, O-glycans and glycolipids. Several siglecs, including sialoadhesin (Sn, siglec-1) and siglec-5, bind to NeuAcalpha2,3Gal, a terminal capping structure that can also be displayed on the lipopolysaccharide (LPS) of Neisseria meningitidis (Nm). In the present study, we examined the potential of siglecs expressed on cells of the immune system to function as receptors for sialylated Nm. We used sialylated and non-sialylated LPS derivatives of two serogroups (A and B) of Nm in this study. Using recombinant chimeric soluble receptors, siglec-transfected cell lines and macrophages from wild-type and Sn-deficient mice, we observed that sialylated but not non-sialylated variants of either genetic background were specifically recognized by Sn and siglec-5, whereas other siglecs examined were ineffective. In addition, macrophages expressing Sn, as well as transfectants expressing Sn or siglec-5, bound and phagocytosed sialylated bacteria in a siglec- and sialic acid-dependent manner. This study demonstrates that Nm LPS sialylation can lead to increased bacterial susceptibility to phagocytic uptake, a phenomenon in direct contrast to previously reported protective effects of LPS sialylation.
authors.affiliation: The Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Jones
authors.forename: Mumtaz
authors.initials: M
authors.lastname: Virji
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D037102:Lectins / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D063267:Sialic Acid Binding Ig-like Lectin 1; D014162:Transfection
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037102:Lectins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C571166:SIGLEC1 protein, human; C114531:SIGLEC5 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse; D019158:N-Acetylneuraminic Acid