Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth

Simple item page
dc.contributor.authorFletcher, Helenen_ZA
dc.contributor.authorKeyser, Alanaen_ZA
dc.contributor.authorBowmaker, Marken_ZA
dc.contributor.authorSayles, Peteren_ZA
dc.contributor.authorKaplan, Gillaen_ZA
dc.contributor.authorHussey, Gregen_ZA
dc.contributor.authorHill, Adrianen_ZA
dc.contributor.authorHanekom, Willemen_ZA
dc.date.accessioned2015-10-30T09:30:54Z
dc.date.available2015-10-30T09:30:54Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: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.en_ZA
dc.identifier.apacitationFletcher, H., Keyser, A., Bowmaker, M., Sayles, P., Kaplan, G., Hussey, G., ... Hanekom, W. (2009). Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth. <i>BMC Medical Genomics</i>, http://hdl.handle.net/11427/14515en_ZA
dc.identifier.chicagocitationFletcher, Helen, Alana Keyser, Mark Bowmaker, Peter Sayles, Gilla Kaplan, Greg Hussey, Adrian Hill, and Willem Hanekom "Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth." <i>BMC Medical Genomics</i> (2009) http://hdl.handle.net/11427/14515en_ZA
dc.identifier.citationFletcher, H. A., Keyser, A., Bowmaker, M., Sayles, P. C., Kaplan, G., Hussey, G., ... & Hanekom, W. A. (2009). Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth. BMC medical genomics, 2(1), 10.en_ZA
dc.identifier.ris TY - Journal Article AU - Fletcher, Helen AU - Keyser, Alana AU - Bowmaker, Mark AU - Sayles, Peter AU - Kaplan, Gilla AU - Hussey, Greg AU - Hill, Adrian AU - Hanekom, Willem AB - 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. DA - 2009 DB - OpenUCT DO - 10.1186/1755-8794-2-10 DP - University of Cape Town J1 - BMC Medical Genomics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth TI - Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth UR - http://hdl.handle.net/11427/14515 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14515
dc.identifier.urihttp://dx.doi.org/10.1186/1755-8794-2-10
dc.identifier.vancouvercitationFletcher H, Keyser A, Bowmaker M, Sayles P, Kaplan G, Hussey G, et al. Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth. BMC Medical Genomics. 2009; http://hdl.handle.net/11427/14515.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2009 Fletcher et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Medical Genomicsen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcmedgenomics/en_ZA
dc.subject.otherBCGen_ZA
dc.subject.otherMycobacteriaen_ZA
dc.subject.otherTuberculosisen_ZA
dc.titleTranscriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birthen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Fletcher_Transcriptional_profiling_2009.pdf
Size:
707.22 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles