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

• Published in: Journal of allergy and clinical immunology Vol. 127; no. 2; pp. 470 - 478.e1
• Main Authors: Tulic, Meri K., BSc, PhD, Hodder, Megan, BSc, Forsberg, Anna, MSc, McCarthy, Suzi, BSc, Richman, Tara, BSc, D’Vaz, Nina, BSc, van den Biggelaar, Anita H.J., BSc, PhD, Thornton, Catherine A., BSc, PhD, Prescott, Susan L., MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-02-2011; Elsevier; Elsevier Limited
• Subjects: Adaptive Immunity; Age Factors; allergic disease; Allergies; Allergy and Immunology; Antigen-Presenting Cells - immunology; Asthma; Biological and medical sciences; Case-Control Studies; Child, Preschool; children; Disease; Eczema; Female; Food; Food allergies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hospitals; Humans; Hypersensitivity - immunology; Immunity, Innate; Immunopathology; Infant; Infant, Newborn; Infections; innate immunity; Ligands; Male; Medical sciences; ontogeny; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T-Lymphocytes - immunology; TECHNOLOGY; TEKNIKVETENSKAP; Toll-like receptor; Toll-Like Receptors - physiology; myeloid dendritic cell; Skin prick test; ontogeny; mDC; pDC; Plasmacytoid dendritic cell; innate immunity; APC; children; Natural killer; SPT; Antigen-presenting cell; TLR; allergic disease; NK; Toll-like receptor; Human; Immunopathology; Allergy; Natural immunity; Toll like receptor; Immunology; Development; Child; Comparative study
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.09.020

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 TH 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 TH 1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific TH 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.