Immune system development during early childhood in tropical Latin America: Evidence for the age-dependent down regulation of the innate immune response

Laboratorio de Investigaciones FEPIS, Quininde, Esmeraldas Province, Ecuador.
Clinical Immunology (Impact Factor: 3.67). 03/2011; 138(3):299-310. DOI: 10.1016/j.clim.2010.12.011
Source: PubMed


The immune response that develops in early childhood underlies the development of inflammatory diseases such as asthma and there are few data from tropical Latin America (LA). This study investigated the effects of age on the development of immunity during the first 5 years of life by comparing innate and adaptive immune responses in Ecuadorian children aged 6-9 months, 22-26 months, and 48-60 months. Percentages of naïve CD4+ T cells declined with age while those of memory CD4(+) and CD8(+) T cells increased indicating active development of the immune system throughout the first five years. Young infants had greater innate immune responses to TLR agonists compared to older children while regulatory responses including SEB-induced IL-10 and percentages of FoxP3(+) T-regulatory cells decreased with age. Enhanced innate immunity in early life may be important for host defense against pathogens but may increase the risk of immunopathology.

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Available from: Laura C Rodrigues, Sep 30, 2015
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    • "Evaluation of the effect of urban vs. rural environment on TLR-induced innate immune responses in infants in South America was the first to reveal striking influence of postnatal environment on innate immunity, with IFNγ and IL-10 production both significantly elevated in urban compared to rural infants (Teran et al., 2011). In European infants, TLR responses differ already at the age of 1 month according to environmental exposure during the first month of life, with concentrations of monocytes negatively associating with breastfeeding and siblings in the home, and positively associating with exposure to pets (Belderbos et al., 2011). "
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    ABSTRACT: The success of the World Health Organization recommended "Expanded Program of Immunization" (EPI) and similar regional or national programs has been astounding. However, infectious threats currently not covered by these programs continue to infect millions of infants around the world. Furthermore, many infants do not receive existing vaccines either on time or for the required number of doses to provide optimal protection. Nor do all infants around the world develop the same protective immune response to the same vaccine. As a result approximately three million infants die every year from vaccine preventable infections. To tackle these issues, new vaccines need to be developed as well as existing ones made easier to administer. This requires identification of age-optimized vaccine schedules and formulations. In order to be most effective this approach will need to take population-based differences in response to vaccines and adjuvants into account. This review summarizes what is currently known about differences between populations around the world in the innate immune response to existing as well as new and promising vaccine adjuvants.
    Frontiers in Immunology 04/2013; 4:81. DOI:10.3389/fimmu.2013.00081
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    • "However, the study by Burl et al. was cross-sectional in nature, and progressive changes in innate immunity over the first year of life could thus have been influenced by inter-individual variability [24]. A similar decline consistent with our findings and those of Burl et al. in TLR induced cytokine production in whole blood was also detected in children born and raised in Ecuador; this decline was observed between 1 and 2 years of age, with no information provided about the earlier time points [23]. However, such decline was not observed in a recent study of infants in Papa New Guinea [22]. "
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    ABSTRACT: The first year of life represents a time of marked susceptibility to infections; this is particularly true for regions in sub-Saharan Africa. As innate immunity directs the adaptive immune response, the observed increased risk for infection as well as a suboptimal response to vaccination in early life may be due to less effective innate immune function. In this study, we followed a longitudinal cohort of infants born and raised in South Africa over the first year of life, employing the most comprehensive analysis of innate immune response to stimulation published to date. Our findings reveal rapid changes in innate immune development over the first year of life. This is the first report depicting dramatic differences in innate immune ontogeny between different populations in the world, with important implications for global vaccination strategies.
    PLoS ONE 09/2012; 7(9):e44763. DOI:10.1371/journal.pone.0044763 · 3.23 Impact Factor
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    • "Gridebacke et al. (33) and Fichizawa et al. (32) found increased expression of CD4+CD25+Foxp3+ Treg cells in the peripheral blood during the first few days of life, followed by stabilization in the level of Treg cells during the first years of life. Furthermore, Teran et al. (34) evaluated a group of children from Latin America and found a significant decrease in the relative amount of Treg cells as age increased. Furthermore, similar to our study, Teran et al. also found variability in the Treg levels in individuals of the same age, indicating that factors such as environment may affect the development of the regulatory arm of the immune system. "
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    ABSTRACT: The purpose of this study was to investigate the association between T cell receptor excision circle levels in peripheral blood mononuclear cells and regulatory T cells that co-express CD25 and Foxp3 in healthy children and adolescents of different ages. The quantification of signal-joint T-cell receptor excision circle levels in the genomic DNA of peripheral blood mononuclear cells was performed using real-time quantitative PCR. The analysis of CD4, CD8, CD25, and Foxp3 expression was performed using flow cytometry. Ninety-five healthy controls (46 females and 49 males) ranging in age from 1 to 18 years were analyzed. The mean T-cell receptor excision circle count in all individuals was 89.095 ± 36.790 T-cell receptor excision circles per microgram of DNA. There was an inverse correlation between T-cell receptor excision circles counts and age (r = -0.846; p<0.001) as well as between the proportion of CD4(+)CD25(+)Foxp3(+) T cells and age (r = -0.467; p = 0.04). In addition, we observed a positive correlation between the amount of CD4(+)CD25(+)Foxp3(+) T cells and the amount of T-cell receptor excision circles per microgram of DNA in individuals of all ages (r = -0.529; p = 0.02). In this study, we observed a decrease in the thymic function with age based on the fact that the level of T-cell receptor excision circles in the peripheral blood positively correlated with the proportion of regulatory T cells in healthy children and adolescents. These findings indicate that although T-cell receptor excision circles and regulatory T cells levels decrease with age, homeostasis of the immune system and relative regulatory T cells population levels are maintained in the peripheral blood.
    Clinics (São Paulo, Brazil) 05/2012; 67(5):425-9. DOI:10.6061/clinics/2012(05)04 · 1.19 Impact Factor
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