Characterization of the Specific Interaction between Sialoadhesin and Sialylated Campylobacter jejuni Lipooligosaccharides

ABSTRACT In Campylobacter jejuni-induced Guillain-Barré syndrome (GBS), molecular mimicry between C. jejuni lipooligosaccharide (LOS) and host gangliosides leads to the production of cross-reactive antibodies directed against the peripheral nerves of the host. Currently, the presence of surface exposed sialylated LOS in C. jejuni is the single known bacterial pathogenesis factor associated with the development of GBS. Using a unique, well-characterized strain collection, we demonstrate that GBS-associated C. jejuni strains bind preferentially to sialoadhesin (Sn, Siglec-1, or CD169), a sialic acid receptor found on a subset of macrophages. In addition, using a whole-cell enzyme-linked immunosorbent assay (ELISA), C. jejuni strains with sialylated LOS bound exclusively to soluble Sn. Mass spectrometry revealed that binding was sialic acid-linkage specific with a preference for α(2,3)-linked sialic acid attached to the terminal galactose of the LOS chain as seen in the gangliosides GD1a, GM1b, and GM3. This molecular interaction was also related to functional consequences as a GBS-associated C. jejuni strain that bound Sn in a whole-cell ELISA adhered to surface-expressed Sn of Sn-transfected CHO cells but was unable to adhere to wild-type CHO cells. Moreover, a sialic acid-negative mutant of the same C. jejuni strain was unable to bind Sn-transfected CHO cells. This is the first report of the preferential binding of GBS-associated C. jejuni strains to the Sn immune receptor (P = 0.014). Moreover, because this binding is dependent on sialylated LOS, the main pathogenic factor in GBS progression, the present findings bring us closer to unraveling the mechanisms that lead to formation of cross-reactive antibodies in GBS disease.

[1]  B. de Bono,et al.  SIGLEC16 encodes a DAP12‐associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non‐functional alleles in humans , 2008, European journal of immunology.

[2]  Xin Liu,et al.  Rapid Method for Sensitive Screening of Oligosaccharide Epitopes in the Lipooligosaccharide from Campylobacter jejuni Strains Isolated from Guillain-Barré Syndrome and Miller Fisher Syndrome Patients , 2008, Journal of Clinical Microbiology.

[3]  Mitsuru Nakamura,et al.  Siglec-15: an immune system Siglec conserved throughout vertebrate evolution. , 2007, Glycobiology.

[4]  J. Laman,et al.  The Guillain-Barré syndrome: a true case of molecular mimicry. , 2004, Trends in immunology.

[5]  P. Crocker.  Siglecs in innate immunity. , 2005, Current opinion in pharmacology.

[6]  H. Endtz,et al.  Characterization of Lipooligosaccharide-Biosynthetic Loci of Campylobacter jejuni Reveals New Lipooligosaccharide Classes: Evidence of Mosaic Organizations , 2008, Journal of bacteriology.

[7]  Jianjun Li,et al.  Structural Characterization of Campylobacter jejuni Lipooligosaccharide Outer Cores Associated with Guillain-Barré and Miller Fisher Syndromes , 2007, Infection and Immunity.

[8]  J. Forrester,et al.  Sialoadhesin Promotes the Inflammatory Response in Experimental Autoimmune Uveoretinitis1 , 2006, The Journal of Immunology.

[9]  T. Phan,et al.  Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells , 2007, Nature Immunology.

[10]  C. Szymanski,et al.  Detection of Conserved N-Linked Glycans and Phase-variable Lipooligosaccharides and Capsules from Campylobacter Cells by Mass Spectrometry and High Resolution Magic Angle Spinning NMR Spectroscopy* , 2003, Journal of Biological Chemistry.

[11]  H. Endtz,et al.  Ganglioside Mimicry of Campylobacter jejuni Lipopolysaccharides Determines Antiganglioside Specificity in Rabbits , 2002, Infection and Immunity.

[12]  H. Endtz,et al.  Origin of ganglioside complex antibodies in Guillain–Barré syndrome , 2007, Journal of Neuroimmunology.

[13]  Eduardo N. Taboada,et al.  The Genetic Bases for the Variation in the Lipo-oligosaccharide of the Mucosal Pathogen, Campylobacter jejuni , 2002, The Journal of Biological Chemistry.

[14]  H. Willison,et al.  Sialic Acid-Binding Immunoglobulin-Like Lectin 7 Mediates Selective Recognition of Sialylated Glycans Expressed on Campylobacter jejuni Lipooligosaccharides , 2006, Infection and Immunity.

[15]  H. Nauwynck,et al.  IFN-alpha treatment enhances porcine Arterivirus infection of monocytes via upregulation of the porcine Arterivirus receptor sialoadhesin. , 2007, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[16]  N. Yuki.  Molecular mimicry between gangliosides and lipopolysaccharides of Campylobacter jejuni isolated from patients with Guillain-Barré syndrome and Miller Fisher syndrome. , 1997, The Journal of infectious diseases.

[17]  M. Moeremans,et al.  Transfer of immune complexes from lymphocytes to follicular dendritic cells , 1986, European journal of immunology.

[18]  L. Pulliam,et al.  Sialoadhesin Expressed on IFN-Induced Monocytes Binds HIV-1 and Enhances Infectivity , 2008, PloS one.

[19]  F. Lopez,et al.  The Membrane-Proximal Immunoreceptor Tyrosine-Based Inhibitory Motif Is Critical for the Inhibitory Signaling Mediated by Siglecs-7 and -9, CD33-Related Siglecs Expressed on Human Monocytes and NK Cells1 , 2004, The Journal of Immunology.

[20]  J. Laman,et al.  Genetic polymorphisms of macrophage-mediators in Guillain–Barré syndrome , 2007, Journal of Neuroimmunology.

[21]  Ajit Varki,et al.  Siglecs and their roles in the immune system , 2007, Nature Reviews Immunology.

[22]  E. Rietschel,et al.  Chemical characterization of Campylobacter jejuni lipopolysaccharides containing N-acetylneuraminic acid and 2,3-diamino-2,3-dideoxy-D-glucose , 1991, Journal of bacteriology.

[23]  H. Willison,et al.  Peripheral neuropathies and anti-glycolipid antibodies. , 2002, Brain : a journal of neurology.

[24]  D. Shotton,et al.  Purification and properties of sialoadhesin, a sialic acid‐binding receptor of murine tissue macrophages. , 1991, The EMBO journal.

[25]  D. Jackson,et al.  Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations. , 2001, Blood.

[26]  Jianjun Li,et al.  Evidence for Acquisition of the Lipooligosaccharide Biosynthesis Locus in Campylobacter jejuni GB11, a Strain Isolated from a Patient with Guillain-Barré Syndrome, by Horizontal Exchange , 2004, Infection and Immunity.

[27]  N. Yuki,et al.  Autoantibodies to GM1b and GalNAc-GD1a: relationship to Campylobacter jejuni infection and acute motor axonal neuropathy in China , 1999, Journal of the Neurological Sciences.

[28]  V. Perry,et al.  The blood-brain barrier regulates the expression of a macrophage sialic acid-binding receptor on microglia. , 1992, Journal of cell science.

[29]  P. Crocker,et al.  Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake , 2003, Molecular Microbiology.

[30]  S. Gordon,et al.  Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin‐like domains. , 1994, The EMBO journal.

[31]  Jianjun Li,et al.  The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome. , 2004, The Journal of clinical investigation.

[32]  H. Endtz,et al.  Cross-reactive antibodies against gangliosides and Campylobacter jejuni lipopolysaccharides in patients with Guillain-Barré or Miller Fisher syndrome. , 1997, The Journal of infectious diseases.

[33]  A. McDonald,et al.  Chemical structures of the core regions of Campylobacter jejuni serotypes O:1, O:4, O:23, and O:36 lipopolysaccharides. , 1993, European journal of biochemistry.

[34]  E. Jones,et al.  Characterization of the Sialic Acid-binding Site in Sialoadhesin by Site-directed Mutagenesis (*) , 1996, The Journal of Biological Chemistry.

[35]  Kazuro Furukawa,et al.  Tolerance to Self Gangliosides Is the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core Oligosaccharides in Campylobacter jejuni Strains Associated with Guillain-Barré Syndrome , 2002, Infection and Immunity.

[36]  Chuan Wu,et al.  Sialoadhesin-Positive Macrophages Bind Regulatory T Cells, Negatively Controlling Their Expansion and Autoimmune Disease Progression1 , 2009, The Journal of Immunology.

[37]  H. Endtz,et al.  The Sialylated Lipooligosaccharide Outer Core in Campylobacter jejuni Is an Important Determinant for Epithelial Cell Invasion , 2008, Infection and Immunity.

[38]  R. Dagan,et al.  Molecular Mimicry in Campylobacter jejuni Lipopolysaccharides and the Development of Guillain-Barré Syndrome , 2010 .

[39]  H. Endtz,et al.  A case of Guillain-Barré syndrome following a family outbreak of Campylobacter jejuni enteritis , 2000, Journal of Neuroimmunology.

[40]  H. Endtz,et al.  A Campylobacter jejuni gene associated with immune-mediated neuropathy , 2001, Nature Medicine.