Document Detail


Age-dependent maturation of Toll-like receptor-mediated cytokine responses in Gambian infants.
MedLine Citation:
PMID:  21533209     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The global burden of neonatal and infant mortality due to infection is staggering, particularly in resource-poor settings. Early childhood vaccination is one of the major interventions that can reduce this burden, but there are specific limitations to inducing effective immunity in early life, including impaired neonatal leukocyte production of Th1-polarizing cytokines to many stimuli. Characterizing the ontogeny of Toll-like receptor (TLR)-mediated innate immune responses in infants may shed light on susceptibility to infection in this vulnerable age group, and provide insights into TLR agonists as candidate adjuvants for improved neonatal vaccines. As little is known about the leukocyte responses of infants in resource-poor settings, we characterized production of Th1-, Th2-, and anti-inflammatory-cytokines in response to agonists of TLRs 1-9 in whole blood from 120 Gambian infants ranging from newborns (cord blood) to 12 months of age. Most of the TLR agonists induced TNFα, IL-1β, IL-6, and IL-10 in cord blood. The greatest TNFα responses were observed for TLR4, -5, and -8 agonists, the highest being the thiazoloquinoline CLO75 (TLR7/8) that also uniquely induced cord blood IFNγ production. For most agonists, TLR-mediated TNFα and IFNγ responses increased from birth to 1 month of age. TLR8 agonists also induced the greatest production of the Th1-polarizing cytokines TNFα and IFNγ throughout the first year of life, although the relative responses to the single TLR8 agonist and the combined TLR7/8 agonist changed with age. In contrast, IL-1β, IL-6, and IL-10 responses to most agonists were robust at birth and remained stable through 12 months of age. These observations provide fresh insights into the ontogeny of innate immunity in African children, and may inform development of age-specific adjuvanted vaccine formulations important for global health.
Authors:
Sarah Burl; John Townend; Jainaba Njie-Jobe; Momodou Cox; Uche J Adetifa; Ebrima Touray; Victoria J Philbin; Christy Mancuso; Beate Kampmann; Hilton Whittle; Assan Jaye; Katie L Flanagan; Ofer Levy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-13
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-08-30     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e18185     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cross-Sectional Studies
Cytokines / secretion*
Gambia
Humans
Immunity, Innate
Infant
Oligonucleotide Array Sequence Analysis
Toll-Like Receptors / physiology*
Grant Support
ID/Acronym/Agency:
MC_U190081990//Medical Research Council; MC_UP_A900_1115//Medical Research Council; MC_UP_A900_1122//Medical Research Council; R01 AI067353-01A1/AI/NIAID NIH HHS; //Medical Research Council
Chemical
Reg. No./Substance:
0/Cytokines; 0/Toll-Like Receptors
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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