Age-dependent maturation of Toll-like receptor-mediated cytokine responses in Gambian infants
| Autor: | Christy J. Mancuso, Ofer Levy, Jainaba Njie-Jobe, Katie L. Flanagan, Victoria J. Philbin, Ebrima S. Touray, Beate Kampmann, John Townend, Sarah Burl, Uche J. Adetifa, Assan Jaye, Hilton Whittle, Momodou Cox |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Agonist
medicine.drug_class Immune Cells Immunology lcsh:Medicine Biology Global Health Pediatrics 03 medical and health sciences Child Development 0302 clinical medicine Immune system Immunity medicine Humans lcsh:Science Immune Response Oligonucleotide Array Sequence Analysis 030304 developmental biology Neonatalology 0303 health sciences Toll-like receptor Multidisciplinary Toll-Like Receptors lcsh:R Child Health Infant TLR7 TLR8 Innate Immunity Immunity Innate 3. Good health Infectious Diseases Cross-Sectional Studies Immune System Cord blood TLR4 Medicine Cytokines Clinical Immunology Gambia lcsh:Q Public Health Research Article 030215 immunology |
| Zdroj: | e18185 PLoS ONE, Vol 6, Iss 4, p e18185 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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