title: Premature infants have impaired airway antiviral IFNγ responses to human metapneumovirus compared to respiratory syncytial virus.
abstract: BACKGROUND
  It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity.
  
  
  METHODS
  Nasal airway secretions were collected from 140 children ≤ 3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay.
  
  
  RESULTS
  Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (< 32 wk gestation) did not exhibit increased Th1/Th2 ratios or elevated nasal airway secretion of IFNγ, CCL5, and IL-10 relative to uninfected controls.
  
  
  CONCLUSIONS
  Our study is the first to demonstrate that premature infants have defective IFNγ, CCL5/RANTES, and IL-10 airway responses during HMPV infection and provides novel insights about the potential reason why HMPV causes severe respiratory disease in children with history of prematurity.
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC.
authors.forename: Krishna
authors.initials: K
authors.lastname: Pancham
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC.|Department of Pediatrics, George Washington University, Washington, DC.|Department of Integrative Systems Biology, George Washington University, Washington, DC.|Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC.
authors.forename: Geovanny F
authors.initials: GF
authors.lastname: Perez
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC.
authors.forename: Shehlanoor
authors.initials: S
authors.lastname: Huseni
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC.
authors.forename: Amisha
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Pediatrics, George Washington University, Washington, DC.
authors.forename: Bassem
authors.initials: B
authors.lastname: Kurdi
authors.affiliation: Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia.|Department of Pediatric Pulmonology and Pediatric Critical Care Medicine, School of Medicine, Universidad El Bosque, Bogota, Colombia.|Research Unit, Military Hospital of Colombia, Bogota, Colombia.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Rodriguez-Martinez
authors.affiliation: Department of Pediatrics, George Washington University, Washington, DC.|Department of Integrative Systems Biology, George Washington University, Washington, DC.|Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC.|Division of Pediatric Otorhinolaryngology, Department of Surgery, George Washington University, Washington, DC.|Division of Pediatric Otorhinolaryngology, Department of Pediatrics, George Washington University, Washington, DC.
authors.forename: Diego
authors.initials: D
authors.lastname: Preciado
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC.|Department of Pediatrics, George Washington University, Washington, DC.|Department of Integrative Systems Biology, George Washington University, Washington, DC.|Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC.|Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Rose
authors.affiliation: Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC.|Department of Pediatrics, George Washington University, Washington, DC.|Department of Integrative Systems Biology, George Washington University, Washington, DC.|Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Nino
mesh_terms: D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005865:Gestational Age; D054884:Host-Pathogen Interactions; D006801:Humans; D007223:Infant; D007234:Infant, Premature; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008297:Male; D029121:Metapneumovirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D018184:Paramyxoviridae Infections / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D011446:Prospective Studies; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D004279:DNA, Viral; C573415:IFNG protein, human; C508609:IL10 protein, human; C508598:IL4 protein, human; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma