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Mrp1 is involved in lipid presentation and iNKT cell activation by Streptococcus pneumoniae.
Chandra, Shilpi; Gray, James; Kiosses, William B; Khurana, Archana; Hitomi, Kaori; Crosby, Catherine M; Chawla, Ashu; Fu, Zheng; Zhao, Meng; Veerapen, Natacha; Richardson, Stewart K; Porcelli, Steven A; Besra, Gurdyal; Howell, Amy R; Sharma, Sonia; Peters, Bjoern; Kronenberg, Mitchell.
Afiliación
  • Chandra S; Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Gray J; The Functional Genomics Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Kiosses WB; Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Khurana A; Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Hitomi K; Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Crosby CM; Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Chawla A; Bioinformatics Core, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Fu Z; Bioinformatics Core, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Zhao M; Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Veerapen N; School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
  • Richardson SK; Department of Chemistry, University of Connecticut, 55N. Eagleville Rd, Storrs, CT, 06269, USA.
  • Porcelli SA; Department of Microbiology and Immunology, and Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
  • Besra G; School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
  • Howell AR; Department of Chemistry, University of Connecticut, 55N. Eagleville Rd, Storrs, CT, 06269, USA.
  • Sharma S; The Functional Genomics Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Peters B; Division of Cellular Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • Kronenberg M; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Nat Commun ; 9(1): 4279, 2018 10 15.
Article en En | MEDLINE | ID: mdl-30323255
Invariant natural killer T cells (iNKT cells) are activated by lipid antigens presented by CD1d, but the pathway leading to lipid antigen presentation remains incompletely characterized. Here we show a whole-genome siRNA screen to elucidate the CD1d presentation pathway. A majority of gene knockdowns that diminish antigen presentation reduced formation of glycolipid-CD1d complexes on the cell surface, including members of the HOPS and ESCRT complexes, genes affecting cytoskeletal rearrangement, and ABC family transporters. We validated the role in vivo for the multidrug resistance protein 1 (Mrp1) in CD1d antigen presentation. Mrp1 deficiency reduces surface clustering of CD1d, which decreased iNKT cell activation. Infected Mrp1 knockout mice show decreased iNKT cell responses to antigens from Streptococcus pneumoniae and were associated with increased mortality. Our results highlight the unique cellular events involved in lipid antigen presentation and show how modification of this pathway can lead to lethal infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Streptococcus pneumoniae / Activación de Linfocitos / Presentación de Antígeno / Células T Asesinas Naturales / Lípidos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Streptococcus pneumoniae / Activación de Linfocitos / Presentación de Antígeno / Células T Asesinas Naturales / Lípidos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido