Differences in innate immune function between allergic and nonallergic children: new insights into immune ontogeny.

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).

CONCLUSION

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.