Flt3 ligand improves the innate response to respiratory syncytial virus and limits lung disease upon RSV reexposure in neonate mice

Autor: Sabine Riffault, Luc Jouneau, Aude Remot, Jérôme Lecardonnel, Daphné Laubreton, Agnès Petit-Camurdan, Catherine Dubuquoy, Delphyne Descamps, Stephan Bouet, Emmanuelle Rebours
Přispěvatelé: UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, ICSA, Project NeoDC [grant number 59000411], Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA)-Université de Tours
Rok vydání: 2015
Předmět:
0301 basic medicine
système immunitaire
viruses
Respiratory syncytial virus
medicine.disease_cause
newborn animal
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Mice
0302 clinical medicine
Neonate
Interferon
Immunology and Allergy
Lung
Mice
Inbred BALB C
Respiratory disease
respiratory system
respiratory disease
virus respiratoire syncytial
3. Good health
Respiratory Syncytial Viruses
Respiratory syncytial virus (RSV)
medicine.anatomical_structure
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Interferon Type I
réponse immunitaire innée
medicine.drug
Signal Transduction
Immunology
Respiratory Syncytial Virus Infections
Biology
Virus
03 medical and health sciences
Immunity
medicine
Animals
Bronchiolitis
Viral
Flt3-L
Cell Proliferation
[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health
nouveau né
Membrane Proteins
Dendritic Cells
Th1 Cells
medicine.disease
Virology
Immunity
Innate
Neonatal infection
Disease Models
Animal
030104 developmental biology
maladie respiratoire
Animals
Newborn
Bronchiolitis
030215 immunology
Zdroj: European Journal of Immunology
European Journal of Immunology, Wiley-VCH Verlag, 2016, 46 (4), pp.874-884. ⟨10.1002/eji.201545929⟩
ISSN: 1521-4141
0014-2980
DOI: 10.1002/eji.201545929⟩
Popis: 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.
Databáze: OpenAIRE
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