Search

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 lessdeveloped 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-c) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-a 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. [ABSTRACT FROM AUTHOR]

To cite this article: Lisciandro JG, Prescott SL, Nadal-Sims MG, Devitt CJ, Pomat W, Siba PM., Holt PG, Strickland D, van den Biggelaar AHJ. Comparison of neonatal T regulatory cell function in Papua New Guinean and Australian newborns. Pediatr Allergy Immunol 2011: Doi: 10.1111/j.1399-3038.2011.01242.x. Abstract Background: Environmental changes, including declining microbial exposure, have been linked with the rising incidence of allergic and autoimmune diseases in 'western' populations. This potentially occurs by altering early development of immuno-regulatory pathways including T regulatory cells (Treg). There is now increasing evidence that such conditioning begins in utero. Methods: We compared neonatal Treg from children born under typical western conditions (Australia, AUS) with those of neonates born under more traditional conditions of high microbial burden (Papua New Guinea, PNG). Results: The frequency of neonatal Treg, defined as CD4+ Foxp3+ CD127− CD25+/high was found to be higher in the cord blood of AUS compared to PNG newborns. However, cord Treg suppressive function in a small subset of children was qualitatively similar between PNG and AUS newborns in both a Treg depletion assay and a Treg supplementation assay. Conclusions: These findings do not support the hypothesis that living in a 'western' versus more traditional environment leads to poor induction or suppressive function of neonatal Treg. However, environmentally-induced immuno-regulation may potentially occur via alternative mechanisms in PNG newborns that should now be investigated further. [ABSTRACT FROM AUTHOR]