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Ontogeny of Toll-Like and NOD-Like Receptor-Mediated innate immune responses in Papua New Guinean infants

Lisciandro, J.G., Prescott, S.L., Nadal-Sims, M.G., Devitt, C.J., Pomat, W., Siba, P.M., Tulic, M.C., Holt, P.G., Strickland, D. and van den Biggelaar, A.H.J. (2012) Ontogeny of Toll-Like and NOD-Like Receptor-Mediated innate immune responses in Papua New Guinean infants. PloS one, 7 (5).

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Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in high-income countries, with little or even no information on other pattern recognition receptors or on early life innate immune responses in children living under very different environmental conditions in less-developed parts of the world. In this study, we describe whole blood innate immune responses to both Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor agonists including the widely used vaccine adjuvant ‘alum’ in a group of Papua New Guinean infants aged 1–3 (n = 18), 4–6 (n = 18), 7–12 (n = 21) and 13–18 (n = 10) months old. Depending on the ligands and cytokines studied, different age-related patterns were found: alum-induced IL-1β and CXCL8 responses were found to significantly decline with increasing age; inflammatory (IL-6, IL-1β, IFN-γ) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-α responses either declined or remained the same. We report for the first time that whole blood innate immune responses to the vaccine adjuvant alum decrease with age in infancy; a finding that may imply that the adjuvant effect of alum in pediatric vaccines could be age-related. Our findings further suggest that patterns of innate immune development may vary between geographically diverse populations, which in line with the ‘hygiene hypothesis’ particularly involves persistence of innate IL-10 responses in populations experiencing higher infectious pressure.

Publication Type: Journal Article
Publisher: Public Library of Science
Copyright: © 2012 Lisciandro et al.
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