Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells

Autor: Darren Sutherland, Juliet Crabtree, Tobias R. Kollmann, Adeline M. Hajjar, Christopher B. Wilson, Nathan Corbett, Arlene Kallos, Stuart E. Turvey, Annie Rein-Weston, Edgardo S. Fortuno, Bing Cai, Darren Blimkie, Kevin Ho, Pascal M. Lavoie, Steven G. Self, Natalie Hawkins
Rok vydání: 2010
Předmět:
Lipopolysaccharides
B Cells
medicine.medical_treatment
Ontogeny
Immunofluorescence
lcsh:Medicine
Stimulation
Pediatrics
Monocytes
Cohort Studies
Child Development
0302 clinical medicine
Young adult
lcsh:Science
Immune Response
0303 health sciences
Toll-like receptor
Multidisciplinary
Toll-Like Receptors
Age Factors
Middle Aged
Innate Immunity
3. Good health
Cytokine
Oligodeoxyribonucleotides
Child
Preschool
Medicine
Cytokines
Research Article
Adult
Immune Cells
Immunology
Antigen-Presenting Cells
Biology
Immune Activation
Immunomodulation
Lipopeptides
Young Adult
03 medical and health sciences
Immune system
Immunity
medicine
Humans
Immunoassays
030304 developmental biology
Inflammation
Innate immune system
lcsh:R
Infant
Newborn
Immunoregulation
Infant
Dendritic Cells
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptor 7
Toll-Like Receptor 8
Toll-Like Receptor 9
Immunologic Techniques
Leukocytes
Mononuclear
Clinical Immunology
lcsh:Q
Developmental Biology
030215 immunology
Zdroj: PLoS ONE, Vol 5, Iss 11, p e15041 (2010)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0015041
Popis: Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an 'immature' neonatal to a 'mature' adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation.
Databáze: OpenAIRE
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