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

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• 作者：Meri K. Tulic BSc ; PhD^a ; ^{mtulic@meddent.uwa.edu.au} ; Megan Hodder BSc^a ; Anna Forsberg MSc^b ; Suzi McCarthy BSc^a ; Tara Richman BSc^a ; Nina D’ ; Vaz BSc^a ; Anita H.J. van den Biggelaar BSc ; PhD^c ; Catherine A. Thornton BSc ; PhD^d ; Susan L. Prescott MD ; PhD^a
• 关键词：Toll-like receptor ; ontogeny ; innate immunity ; allergic disease ; children
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：127
• 期：2
• 页码：470-478.e1
• 全文大小：511 K

文摘

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_H1 (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_H1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific T_H2 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.