title: NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U561, Hôpital Cochin-St Vincent de Paul, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Diana
authors.forename: Thibault
authors.initials: T
authors.lastname: Griseri
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lagaye
authors.forename: Lucie
authors.initials: L
authors.lastname: Beaudoin
authors.forename: Elodie
authors.initials: E
authors.lastname: Autrusseau
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Gautron
authors.forename: Céline
authors.initials: C
authors.lastname: Tomkiewicz
authors.forename: André
authors.initials: A
authors.lastname: Herbelin
authors.forename: Robert
authors.initials: R
authors.lastname: Barouki
authors.forename: Matthias
authors.initials: M
authors.lastname: von Herrath
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.forename: Agnès
authors.initials: A
authors.lastname: Lehuen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D003920:Diabetes Mellitus / Q000209:etiology / Q000276:immunology / Q000821:virology; D008099:Liver / Q000276:immunology / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000150:complications / Q000276:immunology* / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D053278:OX40 Ligand / Q000276:immunology; D009928:Organ Specificity / Q000276:immunology; D010179:Pancreas / Q000276:immunology / Q000821:virology; D053262:Receptors, OX40 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000821:virology; D014779:Virus Replication
chemical_list: D053278:OX40 Ligand; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse