title: Antiviral IFN-γ responses of monocytes at birth predict respiratory tract illness in the first year of life.
abstract: BACKGROUND
  Viral respiratory tract infections are the leading cause of acute illness during infancy and are closely linked to chronic inflammatory airway diseases later in life. However, the determinants of susceptibility to acute respiratory tract infections still need to be defined.
  
  
  OBJECTIVE
  We investigated whether the individual variation in antiviral response at birth determines the risk for acute respiratory tract illness in the first year of life.
  
  
  METHODS
  We studied 82 children who were enrolled in a birth cohort study of inner-city children with at least 1 parent with allergy or asthma. We cultured cord blood monocytes and assessed IFNG and CCL5 mRNA production at 24 hours after inoculation with respiratory syncytial virus. We also monitored the frequency of acute respiratory tract illness at 3-month intervals and analyzed nasal lavage samples for respiratory tract viruses at the time of illness during the first year.
  
  
  RESULTS
  Respiratory tract infection was reported for 88% of subjects, and respiratory tract viruses were recovered in 74% of symptomatic children. We observed a wide range of antiviral responses in cord blood monocytes across the population. Furthermore, a decrease in production of IFNG (but not CCL5) mRNA in response to respiratory syncytial virus infection of monocytes was associated with a significant increase in the frequency of upper respiratory tract infections (r = -0.42, P < .001) and the prevalence of ear and sinus infections, pneumonias, and respiratory-related hospitalizations.
  
  
  CONCLUSIONS
  Individual variations in the innate immune response to respiratory tract viruses are detectable even at birth, and these differences predict the susceptibility to acute respiratory tract illness during the first year of life.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Kaharu
authors.initials: K
authors.lastname: Sumino
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tucker
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahab
authors.forename: Katy F
authors.initials: KF
authors.lastname: Jaffee
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Visness
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bloomberg
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005500:Follow-Up Studies; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology*; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D009035:Mothers; D011247:Pregnancy; D011379:Prognosis; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D012306:Risk; D055815:Young Adult
chemical_list: D018946:Chemokine CCL5; D007371:Interferon-gamma