title: Flt3 ligand improves the innate response to respiratory syncytial virus and limits lung disease upon RSV reexposure in neonate mice.
abstract: Respiratory syncytial virus (RSV) causes severe bronchiolitis in infants worldwide. The immunological factors responsible for RSV susceptibility in infants are poorly understood. Here, we used the BALB/c mouse model of neonatal RSV infection to study the mechanisms leading to severe disease upon reexposure to the virus when adults. Two major deficiencies in neonatal lung innate responses were found: a poor DCs mobilization, and a weak engagement of the IFNI pathway. The administration of Flt3 ligand (Flt3-L), a growth factor that stimulates the proliferation of hematopoietic cells, to neonates before RSV-infection, resulted in increased lung DC number, and reconditioned the IFNI pathway upon RSV neonatal infection. Besides, neonates treated with Flt3-L were protected against exacerbated airway disease upon adult reexposure to RSV. This was associated with a reorientation of RSV-specific responses toward Th1-mediated immunity. Thus, the poor lung DCs and IFNI responses to RSV in neonates may be partly responsible for the deleterious long-term consequences revealed upon adult reexposure to RSV, which could be prevented by Flt3-L treatment. These results open new perspectives for developing neonatal immuno-modulating strategies to reduce the burden of bronchiolitis.
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Remot
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Delphyne
authors.initials: D
authors.lastname: Descamps
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Daphné
authors.initials: D
authors.lastname: Laubreton
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubuquoy
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bouet
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lecardonnel
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Rebours
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Petit-Camurdan
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001990:Bronchiolitis, Viral / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology; D008565:Membrane Proteins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D007370:Interferon Type I; D008565:Membrane Proteins; C084881:flt3 ligand protein
keywords: Dendritic cells; Flt3-L; Interferon; Lung; Neonate; Respiratory syncytial virus