Ontogeny of Toll-like and NOD-like receptor-mediated innate immune responses in Papua New Guinean infants.
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.
Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia. joannel@ichr.uwa.edu.au
Joanne G
JG
Lisciandro
Susan L
SL
Prescott
Marie G
MG
Nadal-Sims
Catherine J
CJ
Devitt
William
W
Pomat
Peter M
PM
Siba
Meri C
MC
Tulic
Patrick G
PG
Holt
Deborah
D
Strickland
Anita H J
AH
van den Biggelaar
D000367:Age Factors; D000534:Alum Compounds; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D007113:Immunity, Innate / Q000502:physiology*; D007223:Infant; D058847:Inflammasomes / Q000378:metabolism* / Q000502:physiology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010219:Papua New Guinea; D018709:Statistics, Nonparametric; D051193:Toll-Like Receptors / Q000819:agonists / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000534:Alum Compounds; D002352:Carrier Proteins; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C041524:aluminum sulfate; D007371:Interferon-gamma