Differences in innate immune function between allergic and nonallergic children: New insights into immune ontogeny - 10/08/11
, 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
Reprint requests: Meri K. Tulic, BSc, PhD, School of Paediatrics and Child Health, Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Perth, Australia.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-⍺, 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).
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.
Le texte complet de cet article est disponible en PDF.Key words : Toll-like receptor, ontogeny, innate immunity, allergic disease, children
Abbreviations used : APC, mDC, NK, pDC, SPT, TLR
Plan
| Supported by the National Health and Medical Research Council (NHMRC) of Australia (grant ID 458502). S. L. P. is supported by an NHMRC Practitioner Fellowship, and M. K. T. is supported by an NHMRC Career Development Award. |
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| Disclosure of potential conflict of interest: M. K. Tulic receives research support from the National Health and Medical Research Council (NHMRC), Australia. C. A. Thornton has received research support from the Welsh Office of Research and Development. S. L. Prescott is on the advisory board for Nestle Nutrition, is a consultant for Fonterra, is a speaker for Nutricia, and receives research support from the National Health and Medical Research Council (NHMRC), Australia. The rest of the authors have declared that they have no conflict of interest. |
Vol 127 - N° 2
P. 470 - février 2011 Retour au numéro
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