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.

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With the emergence of allergic and autoimmune diseases in populations that have started to transit to a western lifestyle, there has been an increasing interest in the role of environmental factors modulating early immune function. Yet, most of the information concerning neonatal immune function has been derived from studies in westernized countries. We postulate that comparative studies of early immune development in children born under conditions that are typical for a westernized vs. that of a still more traditional setting will provide a crucial insight into the environmental-driven immunological mechanisms that are responsible for the world-wide rise in inflammatory disorders. In this review, we summarize the current understanding of early-life immune function in humans in general and the literature on some major lifestyle factors that may influence neonatal immune function and potentially the risk for disease in later life. An understanding of the mechanisms of 'prenatal/early-life programming' in populations living in traditional compared with modern societies is crucial to develop strategies to prevent a further rise in 'western diseases' such as allergic disorders. Indications exist that prenatal conditioning of the innate immune system by low-grade inflammatory responses is key to inducing more tightly regulated postnatal adaptive immune responses.