title: Plasmacytoid dendritic cells during infancy are inversely associated with childhood respiratory tract infections and wheezing.
abstract: BACKGROUND
  It has been proposed that immune dysfunction during early childhood plays an important role in asthma pathogenesis. However, it is not known specifically whether changes in dendritic cells (DCs) during infancy antedate the development of respiratory tract infections, asthma, and related clinical phenotypes.
  
  
  OBJECTIVE
  We sought to assess the association between the level of blood DCs during the first year and the subsequent development of respiratory tract infections, wheezing, and allergic sensitization.
  
  
  METHODS
  A community-based cohort of children with a family history of atopy was followed to age 5 years. Children were monitored intensively for respiratory tract infections. History of wheeze and asthma was collected annually, atopy was documented at 5 years, and flow cytometry was used to identify DC subsets in blood samples collected when children were well.
  
  
  RESULTS
  Levels of plasmacytoid DCs (pDCs) during infancy were inversely correlated with symptoms of lower respiratory tract infections, parent-reported wheezing, and the cumulative rate of physician-diagnosed asthma up to age 5 years. These relationships were independent of atopy, as determined by allergy skin test results and total and specific IgE levels. In contrast, levels of myeloid DCs were not associated with respiratory tract infections, asthma, or wheezing but were associated with total IgE levels at age 5 years.
  
  
  CONCLUSIONS
  In children with a family history of atopy, relative deficiency of circulating pDCs during infancy appears to be a risk factor for more frequent and more severe respiratory tract infections, wheezing, and a diagnosis of asthma. Infants with higher numbers of pDCs are protected against these outcomes.
authors.affiliation: Telethon Institute for Child Health Research, West Perth, and Centre for Child Health Research, University of Western Australia, Perth, Australia. j.upham@uq.edu.au
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
authors.forename: Guicheng
authors.initials: G
authors.lastname: Zhang
authors.forename: Angela
authors.initials: A
authors.lastname: Rate
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Yerkovich
authors.forename: Merci
authors.initials: M
authors.lastname: Kusel
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D002675:Child, Preschool; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D011446:Prospective Studies; D012135:Respiratory Sounds / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology
chemical_list: D007073:Immunoglobulin E