title: Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.
abstract: BACKGROUND
  Microbial products are of central interest in the modulation of allergic propensity.
  
  
  OBJECTIVE
  We sought to explore whether allergic children show differences in microbial Toll-like receptor (TLR)-mediated responses over their first 5 years of life.
  
  
  METHODS
  Mononuclear cells isolated from 35 allergic and 35 nonallergic children at birth and 1, 2.5, and 5 years of age were stimulated with TLR2-TLR9 ligands to study innate immune function and with allergens or mitogen to assess adaptive T-cell responses. Cytokine production was measured by using Luminex multiplexing technology.
  
  
  RESULTS
  Nonallergic children show progressive and significant age-related increases in innate cytokine responses (IL-1β, IL-6, TNF-α, and IL-10) to virtually all TLR ligands. This innate maturation corresponds with a parallel increase in adaptive T(H)1 (IFN-γ) responses to allergens and mitogens. In contrast, allergic children show exaggerated innate responses at birth (P < .01) but a relative decrease with age thereafter, so that by age 5 years, TLR responses are attenuated compared with those seen in nonallergic subjects (P < .05). This early hyperresponsiveness in allergic subjects fails to translate to a corresponding maturation of T(H)1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific T(H)2 responses (P < .01).
  
  
  CONCLUSIONS
  Our findings suggest significant differences in the developmental trajectory of innate immune function in children with allergic disease that might contribute to the recognized differences in postnatal adaptive T-cell immunity.
authors.affiliation: Childhood Allergy and Immunology Research, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. mtulic@meddent.uwa.edu.au
authors.forename: Meri K
authors.initials: MK
authors.lastname: Tulic
authors.forename: Megan
authors.initials: M
authors.lastname: Hodder
authors.forename: Anna
authors.initials: A
authors.lastname: Forsberg
authors.forename: Suzi
authors.initials: S
authors.lastname: McCarthy
authors.forename: Tara
authors.initials: T
authors.lastname: Richman
authors.forename: Nina
authors.initials: N
authors.lastname: D'Vaz
authors.forename: Anita H J
authors.initials: AH
authors.lastname: van den Biggelaar
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Thornton
authors.forename: Susan L
authors.initials: SL
authors.lastname: Prescott
mesh_terms: D056704:Adaptive Immunity; D000367:Age Factors; D000938:Antigen-Presenting Cells / Q000276:immunology; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007113:Immunity, Innate; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D051193:Toll-Like Receptors