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Dectin-2 Recognizes Mannosylated O-antigens of Human Opportunistic Pathogens and Augments Lipopolysaccharide Activation of Myeloid Cells.
Wittmann, Alexandra; Lamprinaki, Dimitra; Bowles, Kristian M; Katzenellenbogen, Ewa; Knirel, Yuriy A; Whitfield, Chris; Nishimura, Takashi; Matsumoto, Naoki; Yamamoto, Kazuo; Iwakura, Yoichiro; Saijo, Shinobu; Kawasaki, Norihito.
Afiliación
  • Wittmann A; From the Food and Health Institute Strategic Programme, Institute of Food Research, Norwich NR4 7UA, United Kingdom.
  • Lamprinaki D; From the Food and Health Institute Strategic Programme, Institute of Food Research, Norwich NR4 7UA, United Kingdom.
  • Bowles KM; Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
  • Katzenellenbogen E; the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw 53-114, Poland.
  • Knirel YA; the N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia.
  • Whitfield C; the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
  • Nishimura T; the Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba 277-8562, Japan.
  • Matsumoto N; the Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba 277-8562, Japan.
  • Yamamoto K; the Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba 277-8562, Japan.
  • Iwakura Y; the Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan, and.
  • Saijo S; the Department of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
  • Kawasaki N; From the Food and Health Institute Strategic Programme, Institute of Food Research, Norwich NR4 7UA, United Kingdom, the Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Chiba 277-8562, Japan, norihito.kawasaki@ifr.ac.uk.
J Biol Chem ; 291(34): 17629-38, 2016 08 19.
Article en En | MEDLINE | ID: mdl-27358401
LPS consists of a relatively conserved region of lipid A and core oligosaccharide and a highly variable region of O-antigen polysaccharide. Whereas lipid A is known to bind to the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, the role of the O-antigen remains unclear. Here we report a novel molecular interaction between dendritic cell-associated C-type lectin-2 (Dectin-2) and mannosylated O-antigen found in a human opportunistic pathogen, Hafnia alvei PCM 1223, which has a repeating unit of [-Man-α1,3-Man-α1,2-Man-α1,2-Man-α1,2-Man-α1,3-]. H. alvei LPS induced higher levels of TNFα and IL-10 from mouse bone marrow-derived dendritic cells (BM-DCs), when compared with Salmonella enterica O66 LPS, which has a repeat of [-Gal-α1,6-Gal-α1,4-[Glc-ß1,3]GalNAc-α1,3-GalNAc-ß1,3-]. In a cell-based reporter assay, Dectin-2 was shown to recognize H. alvei LPS. This binding was inhibited by mannosidase treatment of H. alvei LPS and by mutations in the carbohydrate-binding domain of Dectin-2, demonstrating that H. alvei LPS is a novel glycan ligand of Dectin-2. The enhanced cytokine production by H. alvei LPS was Dectin-2-dependent, because Dectin-2 knock-out BM-DCs failed to do so. This receptor cross-talk between Dectin-2 and TLR4 involved events including spleen tyrosine kinase (Syk) activation and receptor juxtaposition. Furthermore, another mannosylated LPS from Escherichia coli O9a also bound to Dectin-2 and augmented TLR4 activation of BM-DCs. Taken together, these data indicate that mannosylated O-antigens from several Gram-negative bacteria augment TLR4 responses through interaction with Dectin-2.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos O / Células Mieloides / Lectinas Tipo C / Bacterias Gramnegativas Límite: Animals / Humans / Male Idioma: En Revista: J Biol Chem Año: 2016 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos O / Células Mieloides / Lectinas Tipo C / Bacterias Gramnegativas Límite: Animals / Humans / Male Idioma: En Revista: J Biol Chem Año: 2016 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos