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TLR9-mediated dendritic cell activation uncovers mammalian ganglioside species with specific ceramide backbones that activate invariant natural killer T cells.
Paget, Christophe; Deng, Shenglou; Soulard, Daphnée; Priestman, David A; Speca, Silvia; von Gerichten, Johanna; Speak, Anneliese O; Saroha, Ashish; Pewzner-Jung, Yael; Futerman, Anthony H; Mallevaey, Thierry; Faveeuw, Christelle; Gu, Xiaobo; Platt, Frances M; Sandhoff, Roger; Trottein, François.
Afiliación
  • Paget C; Univ. Lille, Centre d'Infection et d'Immunité de Lille, Lille, France.
  • Deng S; Centre National de la Recherche Scientifique, Lille, France.
  • Soulard D; Institut National de la Santé et de la Recherche Médicale, Lille, France.
  • Priestman DA; Centre Hospitalier Universitaire de Lille, Lille, France.
  • Speca S; Institut Pasteur de Lille, Lille, France.
  • von Gerichten J; Institut National de la Santé et de la Recherche Médicale, Centre d'Etude des Pathologies Respiratoires (CEPR), Faculté de Médecine, Université de Tours, Tours, France.
  • Speak AO; Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.
  • Saroha A; S&D Lipopharma LLC, Provo, Utah, United States of America.
  • Pewzner-Jung Y; Univ. Lille, Centre d'Infection et d'Immunité de Lille, Lille, France.
  • Futerman AH; Centre National de la Recherche Scientifique, Lille, France.
  • Mallevaey T; Institut National de la Santé et de la Recherche Médicale, Lille, France.
  • Faveeuw C; Centre Hospitalier Universitaire de Lille, Lille, France.
  • Gu X; Institut Pasteur de Lille, Lille, France.
  • Platt FM; Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
  • Sandhoff R; Institut National de la Santé et de la Recherche Médicale, Lille Inflammation Research International Center, Lille, France.
  • Trottein F; Lipid Pathobiochemistry Group German Cancer Research Center, Heidelberg, Germany.
PLoS Biol ; 17(3): e3000169, 2019 03.
Article en En | MEDLINE | ID: mdl-30822302
ABSTRACT
CD1d-restricted invariant natural killer T (iNKT) cells represent a heterogeneous population of lipid-reactive T cells that are involved in many immune responses, mediated through T-cell receptor (TCR)-dependent and/or independent activation. Although numerous microbial lipid antigens (Ags) have been identified, several lines of evidence have suggested the existence of relevant Ags of endogenous origin. However, the identification of their precise nature as well as the molecular mechanisms involved in their generation are still highly controversial and ill defined. Here, we identified two mammalian gangliosides-namely monosialoganglioside GM3 and disialoganglioside GD3-as endogenous activators for mouse iNKT cells. These glycosphingolipids are found in Toll-like receptor-stimulated dendritic cells (DC) as several species varying in their N-acyl fatty chain composition. Interestingly, their ability to activate iNKT cells is highly dependent on the ceramide backbone structure. Thus, both synthetic GM3 and GD3 comprising a d181-C241 ceramide backbone were able to activate iNKT cells in a CD1d-dependent manner. GM3 and GD3 are not directly recognized by the iNKT TCR and required the Ag presenting cell intracellular machinery to reveal their antigenicity. We propose a new concept in which iNKT cells can rapidly respond to pre-existing self-molecules after stress-induced structural changes in CD1d-expressing cells. Moreover, these gangliosides conferred partial protection in the context of bacterial infection. Thus, this report identified new biologically relevant lipid self-Ags for iNKT cells.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ceramidas / Receptor Toll-Like 9 / Células T Asesinas Naturales / Gangliósidos Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ceramidas / Receptor Toll-Like 9 / Células T Asesinas Naturales / Gangliósidos Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Francia