Natural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement.
Plasmacytoid dendritic cells (pDC) are specialized in secretion of type I interferon in response to pathogens. Here we show that natural monoamines and synthetic amines inhibit pDC activation by RNA viruses. Furthermore, a synthetic analogue of histamine reduces type I interferon production in a mouse model of influenza infection. We identify CXC chemokine receptor 4 (CXCR4) as a receptor used by amines to inhibit pDC. Our study establishes a functional link between natural amines and the innate immune system and identifies CXCR4 as a potential 'on-off' switch of pDC activity with therapeutic potential.
CNRS UMR-8601, Université Paris Descartes, CICB, 45 rue des Saints-Pères, 75006 Paris, France.|Team Chemistry &Biology, Modeling &Immunology for Therapy, CBMIT.
Nikaïa
N
Smith
CNRS UMR-8601, Université Paris Descartes, CICB, 45 rue des Saints-Pères, 75006 Paris, France.|Team Chemistry &Biology, Modeling &Immunology for Therapy, CBMIT.
Nicolas
N
Pietrancosta
Immunoregulation Laboratory, Francis Crick Institute, London NW1 1AT, UK.
Sophia
S
Davidson
INSERM UMR-S 1124, Université Paris Descartes, 45 rue des Saints-Pères, 75006 Paris, France.
Jacques
J
Dutrieux
Institut Pasteur, Virus &Immunity Unit, 25-28 Rue du Dr Roux, Paris 75015, France.
Lise
L
Chauveau
Inflammation Chimiokines et Immunopathologie, INSERM, Faculté de médecine-Université Paris-Sud, Université Paris-Saclay, 92140 Clamart, France.
Pasquale
P
Cutolo
CNRS UMR-8147, Hôpital Necker, 156 Rue de Vaugirard, 75015 Paris, France.
Michel
M
Dy
Institut Pasteur, Unité de Régulation des Infections Rétrovirales, 25-28 Rue du Dr Roux, Paris 75015, France.
Daniel
D
Scott-Algara
INSERM U1151, CNRS8253, Université Paris Descartes, Hôpital Necker, 156 Rue de Vaugirard, 75015 Paris, France.
Bénédicte
B
Manoury
Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.
Onofrio
O
Zirafi
CNRS UMR-8601, Université Paris Descartes, CICB, 45 rue des Saints-Pères, 75006 Paris, France.
Isabelle
I
McCort-Tranchepain
Institut de Génomique Fonctionnelle, CNRS UMR5203, INSERM U661, Université de Montpellier (IFR3), 141 rue de la Cardonille, F-34094 Montpellier Cedex 5, France.
Thierry
T
Durroux
Inflammation Chimiokines et Immunopathologie, INSERM, Faculté de médecine-Université Paris-Sud, Université Paris-Saclay, 92140 Clamart, France.
Françoise
F
Bachelerie
Institut Pasteur, Virus &Immunity Unit, 25-28 Rue du Dr Roux, Paris 75015, France.
Olivier
0000-0002-0729-1475
O
Schwartz
Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.
Jan
J
Münch
Immunoregulation Laboratory, Francis Crick Institute, London NW1 1AT, UK.
Andreas
0000-0001-5226-2991
A
Wack
INSERM UMR-S 1124, Université Paris Descartes, 45 rue des Saints-Pères, 75006 Paris, France.
Sébastien
S
Nisole
CNRS UMR-8601, Université Paris Descartes, CICB, 45 rue des Saints-Pères, 75006 Paris, France.|Team Chemistry &Biology, Modeling &Immunology for Therapy, CBMIT.
Jean-Philippe
JP
Herbeuval
D000588:Amines / Q000494:pharmacology*; D064751:Ammonium Compounds / Q000737:chemistry; D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D006678:HIV / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007370:Interferon Type I / Q000378:metabolism; D051379:Mice; D009975:Orthomyxoviridae / Q000502:physiology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000588:Amines; D064751:Ammonium Compounds; D007093:Imidazoles; D007370:Interferon Type I; D019718:Receptors, CXCR4; D011968:Receptors, Histamine; D053221:TNF-Related Apoptosis-Inducing Ligand; D006632:Histamine; D013890:Thiourea; C086108:clobenpropit