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Acquisition of Adult-Like TLR4 and TLR9 Responses during the First Year of Life
- Source :
- PLoS ONE, PLoS ONE, Vol 5, Iss 4, p e10407 (2010)
- Publication Year :
- 2010
- Publisher :
- Public Library of Science, 2010.
-
Abstract
- BACKGROUND: Characteristics of the human neonatal immune system are thought to be responsible for heightened susceptibility to infectious pathogens and poor responses to vaccine antigens. Using cord blood as a source of immune cells, many reports indicate that the response of neonatal monocytes and dendritic cells (DC) to Toll-like receptor (TLR) agonists differs significantly from that of adult cells. Herein, we analyzed the evolution of these responses within the first year of life. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples from children (0, 3, 6, 9, 12 month old) and healthy adults were stimulated ex vivo with bacterial lipopolysaccharide (LPS, TLR4 agonist) or CpG oligonucleotides (TLR9 agonist). We determined phenotypic maturation of monocytes, myeloid (m) and plasmacytoid (p) DC and production of cytokines in the culture supernatants. We observed that surface expression of CD80 and HLA-DR reaches adult levels within the first 3 months of life for mDCs and 6-9 months of life for monocytes and pDCs. In response to LPS, production of TNF-alpha, IP-10 and IL-12p70 reached adult levels between 6-9 months of life. In response to CpG stimulation, production of type I IFN-dependent chemokines (IP-10 and CXCL9) gradually increased with age but was still limited in 1-year old infants as compared to adult controls. Finally, cord blood samples stimulated with CpG ODN produced large amounts of IL-6, IL-8, IL-1beta and IL-10, a situation that was not observed for 3 month-old infants. CONCLUSIONS: The first year of life represents a critical period during which adult-like levels of TLR responses are reached for most but not all cytokine responses.
- Subjects :
- Adult
Lipopolysaccharides
Human Development
Immunology/Innate Immunity
lcsh:Medicine
First year of life
Biology
Vaccine antigen
Monocytes
Immune system
Humans
lcsh:Science
Receptor
Child
Cells, Cultured
Multidisciplinary
lcsh:R
TLR9
Infant
Dendritic Cells
Fetal Blood
Toll-Like Receptor 9
Toll-Like Receptor 4
Oligodeoxyribonucleotides
Cord blood
Immune System
Immunology
TLR4
Cytokines
lcsh:Q
Human medicine
Pediatrics and Child Health/Neonatology
Immunology/Leukocyte Development
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....08be3ba1a0d9628cbe57ce45dee144f6