Authors:
Tulic, M. K.; Hodder, M.; Forsberg, A.; Van Den Biggelaar, A. H. J.; et al.
Authors notes:
Journal of Allergy and Clinical Immunology. 2011;127(2):470-8.e1
Keywords:
allergic disease, children, innate immunity, ontogeny, Toll-like receptor
Abstract:
Microbial products are of central interest in the modulation of allergic propensity. We sought to explore whether allergic children show differences in microbial Toll-like receptor (TLR)-mediated responses over their first 5 years of life.
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.
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 TH1 (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 TH1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific TH2 responses (P < .01).
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. © 2010 American Academy of Allergy, Asthma & Immunology.