NKT cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner.
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.
Diana
Julien
J
Institut National de la Santé et de la Recherche Médicale U561, Hôpital Cochin-St Vincent de Paul, Paris, France.
Griseri
Thibault
T
Lagaye
Sylvie
S
Beaudoin
Lucie
L
Autrusseau
Elodie
E
Gautron
Anne-Sophie
AS
Tomkiewicz
Céline
C
Herbelin
André
A
Barouki
Robert
R
von Herrath
Matthias
M
Dalod
Marc
M
Lehuen
Agnès
A
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
D053278:OX40 Ligand; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse