title: Responsiveness to respiratory syncytial virus in neonates is mediated through thymic stromal lymphopoietin and OX40 ligand.
abstract: BACKGROUND
  Recent studies revealed a critical role for thymic stromal lymphopoietin (TSLP) released from epithelial cells and OX40 ligand (OX40L) expressed on dendritic cells (DCs) in T(H)2 priming and polarization.
  
  
  OBJECTIVE
  We sought to determine the importance of the TSLP-OX40L axis in neonatal respiratory syncytial virus (RSV) infection.
  
  
  METHODS
  Mice were initially infected with RSV as neonates or adults and reinfected 5 weeks later. Anti-OX40L or anti-TSLP were administered during primary or secondary infection. Outcomes included assessment of airway function and inflammation and expression of OX40L, TSLP, and IL-12.
  
  
  RESULTS
  OX40L was expressed mainly on CD11c(+)MHC class II (MHCII)(+)CD11b(+) DCs but not CD103(+) DCs. Treatment of neonates with OX40L antibody during primary RSV infection prevented the subsequent enhancement of airway hyperresponsiveness and the development of airway eosinophilia and mucus hyperproduction on reinfection. Administration of anti-TSLP before neonatal RSV infection reduced the accumulation of lung DCs, decreased OX40L expression on lung DCs, and attenuated the enhancement of airway responses after reinfection.
  
  
  CONCLUSIONS
  In mice initially infected as neonates, TSLP expression induced by RSV infection is an important upstream event that controls OX40L expression, lung DC migration, and T(H)2 polarization, accounting for the enhanced response on reinfection.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA.
authors.forename: Junyan
authors.initials: J
authors.lastname: Han
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Yi
authors.initials: Y
authors.lastname: Jia
authors.forename: Meiqin
authors.initials: M
authors.lastname: Wang
authors.forename: Wanjiang
authors.initials: W
authors.lastname: Zeng
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Okamoto
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019138:Antibodies, Blocking / Q000008:administration & dosage; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D053278:OX40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D019138:Antibodies, Blocking; D016207:Cytokines; D053278:OX40 Ligand; D018664:Interleukin-12; D000094632:Thymic Stromal Lymphopoietin