Human Gene Set: FLETCHER_PBMC_BCG_10W_INFANT_BCG_STIMULATED_VS_UNSTIMULATED_10W_UP

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Standard name FLETCHER_PBMC_BCG_10W_INFANT_BCG_STIMULATED_VS_UNSTIMULATED_10W_UP
Systematic name M41041
Brief description Genes up-regulated in peripheral blood mononuclear cell stimulated vs unstimulated in infants (10w) after exposure to BCG (Danish strain BCG Statens Serum Institut, Denmark) , time point 10W. Comment: PBMCs drawn at 10 weeks following immunization at birth
Full description or abstract BACKGROUND: Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guerin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. However, our understanding of the complexity of immunity to BCG in infants is inadequate, making interpretation of vaccine-induced immune responses difficult. METHODS: To better understand BCG-induced immunity, we performed gene expression profiling in five 10-week old infants routinely vaccinated with BCG at birth. RNA was extracted from 12 hour BCG-stimulated or purified protein derivative of tuberculin (PPD)-stimulated PBMC, isolated from neonatal blood collected 10 weeks after vaccination. RNA was hybridised to the Sentrix(R) HumanRef-8 Expression BeadChip (Illumina) to measure expression of > 16,000 genes. RESULTS: We found that ex vivo stimulation of PBMC with PPD and BCG induced largely similar gene expression profiles, except that BCG induced greater macrophage activation. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, including PPAR-gamma, involved in activation of the alternative, anti-inflammatory macrophage response was down-regulated following stimulation with both antigens. In contrast, up-regulation of genes associated with the classic, pro-inflammatory macrophage response was noted. Further analysis revealed a decrease in the expression of cell adhesion molecules (CAMs), including integrin alpha M (ITGAM), which is known to be important for entry of mycobacteria into the macrophage. Interestingly, more leukocyte genes were down-regulated than up-regulated. CONCLUSION: Our results suggest that a combination of suppressed and up-regulated genes may be key in determining development of protective immunity to TB induced by vaccination with BCG.
Collection C7: Immunologic Signature
      VAX: HIPC Vaccine Response
Source publication Pubmed 19239680   Authors: Fletcher HA,Keyser A,Bowmaker M,Sayles PC,Kaplan G,Hussey G,Hill AV,Hanekom WA
Exact source Additional File 2, Tab A BCG
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External links https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654906/bin/1755-8794-2-10-S2.xls
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Organism Homo sapiens
Contributed by HIPC SIGNATURES (NIAID/HIPC SIGNATURES)
Source platform HUMAN_GENE_SYMBOL
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