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Ontogeny of Toll-like and NOD-like receptor-mediated innate immune responses in Papua New Guinean infants.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (5), pp. e36793. Date of Electronic Publication: 2012 May 23. - Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Age Factors
Alum Compounds
Cells, Cultured
Cross-Sectional Studies
Humans
Infant
Inflammasomes physiology
Interferon-gamma blood
Interleukin-10 blood
Interleukin-1beta blood
Interleukin-6 blood
Leukocytes, Mononuclear
NLR Family, Pyrin Domain-Containing 3 Protein
Papua New Guinea
Statistics, Nonparametric
Toll-Like Receptors agonists
Tumor Necrosis Factor-alpha blood
Carrier Proteins physiology
Immune System growth & development
Immunity, Innate physiology
Inflammasomes metabolism
Toll-Like Receptors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22649499
- Full Text :
- https://doi.org/10.1371/journal.pone.0036793