Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of South African Infants throughout the First Year of Life

Abstract

The first year of life represents a time of marked susceptibility to infections; this is particularly true for regions in sub-Saharan Africa. As innate immunity directs the adaptive immune response, the observed increased risk for infection as well as a suboptimal response to vaccination in early life may be due to less effective innate immune function. In this study, we followed a longitudinal cohort of infants born and raised in South Africa over the first year of life, employing the most comprehensive analysis of innate immune response to stimulation published to date. Our findings reveal rapid changes in innate immune development over the first year of life. This is the first report depicting dramatic differences in innate immune ontogeny between different populations in the world, with important implications for global vaccination strategies.

Influence of the microbiota on vaccine effectiveness

“…In support of this hypothesis, there is a significant difference in T helper (Th)1 cytokine responsiveness to classical TLR agonists in children from poor regions of South Africa as compared to Canadian children [37]. Most strikingly, immune cells in the blood of South African infants aged 2 years are severely hyporesponsive to lipopolysaccharide (LPS) stimulation and secrete low levels of cytokines in response to TLR4 stimulation compared to age-matched children from Canada [38].…”

Dectin-1 activation unlocks IL12A expression and reveals the TH1 potency of neonatal dendritic cells

“…The completed phase III trial showed only modest efficacy, with an overall 30% protection against severe malaria. 7 Past studies emphasized the gradual acquisition of TLR responsiveness in newborns and infants in whole blood and PBMCs, 8,9 with an age-dependent maturation of IL-12p70 secretion capability throughout childhood. 10 These studies also show that neonatal immune cells seem to produce more IL-10 and T H 17-polarizing cytokines (IL-6, IL-1B, and IL-23) after TLR stimulation.…”

The seroprevalence ofBordetella pertussisantibodies in adolescents in the Western Cape

“…The question remains as to whether or not subsequent seropositivity against pertussis or any other pathogen equates to actual protection against the disease. 24,[28][29][30] The assay that was used in this study was unable to distinguish between IgG antibodies produced as a result of primary infection or vaccination. Furthermore, while PT is exclusively secreted by B. pertussis, FHA is also secreted by B. parapertussis and B. bronchiseptica.…”