1. NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner
- Author
-
André Herbelin, Céline Tomkiewicz, Agnès Lehuen, Julien Diana, Thibault Griseri, Anne-Sophie Gautron, Lucie Beaudoin, Matthias von Herrath, Robert Barouki, Marc Dalod, Sylvie Lagaye, Elodie Autrusseau, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Slama, Catherine, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Pharmacologie, toxicologie et signalisation cellulaire (U747), La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Cochin [AP-HP], Physiologie Cellulaire des Regulations Hormonales, Nutritionnelles et Pharmacologiques, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), La Jolla Institute for Allergy and Immunology (LIA), La Jolla Institute for Allergy & Immunology, and Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
- Subjects
MESH: Signal Transduction ,MESH: Spleen ,Plasmacytoid dendritic cell ,CD8-Positive T-Lymphocytes ,Virus Replication ,Mice ,0302 clinical medicine ,Interferon ,Immunology and Allergy ,Lymphocytic choriomeningitis virus ,MESH: Animals ,MESH : Pancreas ,MESH: Organ Specificity ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,MESH: Dendritic Cells ,hemic and immune systems ,MESH : CD8-Positive T-Lymphocytes ,MESH: Pancreas ,MESH: Receptors, OX40 ,Acquired immune system ,MESH: CD8-Positive T-Lymphocytes ,3. Good health ,MESH : Virus Replication ,MESH : Diabetes Mellitus ,medicine.anatomical_structure ,Infectious Diseases ,Liver ,Organ Specificity ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,MESH: Lymphocytic choriomeningitis virus ,medicine.drug ,Signal Transduction ,MESH : Spleen ,MESH : Lymphocytic Choriomeningitis ,MESH: Diabetes Mellitus ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,MESH: Lymphocytic Choriomeningitis ,Immunology ,Spleen ,OX40 Ligand ,Biology ,Lymphocytic Choriomeningitis ,Lymphocytic choriomeningitis ,MESH: OX40 Ligand ,MESH : Lymphocytic choriomeningitis virus ,MESH : Organ Specificity ,03 medical and health sciences ,Immune system ,MESH : Mice ,medicine ,Diabetes Mellitus ,Animals ,MESH : OX40 Ligand ,MESH: Mice ,Pancreas ,030304 developmental biology ,MESH : Signal Transduction ,MESH: Virus Replication ,MESH : Liver ,Dendritic Cells ,Receptors, OX40 ,medicine.disease ,MESH : Natural Killer T-Cells ,Viral replication ,MESH: Natural Killer T-Cells ,CELLIMMUNO ,MESH : Dendritic Cells ,Natural Killer T-Cells ,MESH : Animals ,MESH : Receptors, OX40 ,CD8 ,030215 immunology ,MESH: Liver - Abstract
International audience; Invariant natural killer T (iNKT) cells promote immune responses to various pathogens, but exactly how iNKT cells control antiviral responses is unclear. Here, we showed that iNKT cells induced tissue-specific antiviral effects in mice infected by lymphocytic choriomeningitis virus (LCMV). Indeed, iNKT cells inhibited viral replication in the pancreas and liver but not in the spleen. In the pancreas, iNKT cells expressed the OX40 molecule and promoted type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) through OX40-OX40 ligand interaction. Subsequently, this iNKT cell-pDC cooperation attenuated the antiviral adaptive immune response in the pancreas but not in the spleen. The dampening of pancreatic anti-LCMV CD8(+) T cell response prevented tissue damage in transgenic mice expressing LCMV protein in islet beta cells. Thus, this study identifies pDCs as an essential partner of iNKT cells for mounting an efficient, nondeleterious antiviral response in peripheral tissue.
- Published
- 2007