Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study

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dc.contributor.authorSubbian, Selvakumaren_ZA
dc.contributor.authorTsenova, Lianaen_ZA
dc.contributor.authorKim, Mi-Jeongen_ZA
dc.contributor.authorWainwright, Helen Cen_ZA
dc.contributor.authorVisser, Annalieen_ZA
dc.contributor.authorBandyopadhyay, Nirmalyaen_ZA
dc.contributor.authorBader, Joel Sen_ZA
dc.contributor.authorKarakousis, Petros Cen_ZA
dc.contributor.authorMurrmann, Gabriele Ben_ZA
dc.contributor.authorBekker, Linda-Gailen_ZA
dc.date.accessioned2015-11-23T12:32:36Z
dc.date.available2015-11-23T12:32:36Z
dc.date.issued2015en_ZA
dc.description.abstractThe formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different granulomas share core similarities in their immunological/inflammatory characteristics, they also exhibit significant divergence. Despite similar numbers of CD68 + macrophages in the different lesions, the extent of immune reactivity, as determined by the density of CD3 + T cells in the macrophage rich areas, and the extent of fibrosis, shows considerable variation. Both quantitative and qualitative differences among significantly differentially expressed genes (SDEG) were noted in each of the lesion types studied. Further, network/pathway analysis of SDEG revealed differential regulation of inflammatory response, immune cell trafficking, and cell mediated immune response in the different lesions. Our data highlight the formidable challenges facing ongoing efforts to identify peripheral blood biomarkers due to the diversity of lesion types and complexity of local immune responses in the lung.en_ZA
dc.identifier.apacitationSubbian, S., Tsenova, L., Kim, M., Wainwright, H. C., Visser, A., Bandyopadhyay, N., ... Bekker, L. (2015). Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study. <i>PLoS One</i>, http://hdl.handle.net/11427/15315en_ZA
dc.identifier.chicagocitationSubbian, Selvakumar, Liana Tsenova, Mi-Jeong Kim, Helen C Wainwright, Annalie Visser, Nirmalya Bandyopadhyay, Joel S Bader, Petros C Karakousis, Gabriele B Murrmann, and Linda-Gail Bekker "Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/15315en_ZA
dc.identifier.citationSubbian, S., Tsenova, L., Kim, M. J., Wainwright, H. C., Visser, A., Bandyopadhyay, N., ... & Kaplan, G. (2015). Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study. PloS one, 10(7), e0132249. doi:10.1371/journal.pone.0132249en_ZA
dc.identifier.ris TY - Journal Article AU - Subbian, Selvakumar AU - Tsenova, Liana AU - Kim, Mi-Jeong AU - Wainwright, Helen C AU - Visser, Annalie AU - Bandyopadhyay, Nirmalya AU - Bader, Joel S AU - Karakousis, Petros C AU - Murrmann, Gabriele B AU - Bekker, Linda-Gail AB - The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different granulomas share core similarities in their immunological/inflammatory characteristics, they also exhibit significant divergence. Despite similar numbers of CD68 + macrophages in the different lesions, the extent of immune reactivity, as determined by the density of CD3 + T cells in the macrophage rich areas, and the extent of fibrosis, shows considerable variation. Both quantitative and qualitative differences among significantly differentially expressed genes (SDEG) were noted in each of the lesion types studied. Further, network/pathway analysis of SDEG revealed differential regulation of inflammatory response, immune cell trafficking, and cell mediated immune response in the different lesions. Our data highlight the formidable challenges facing ongoing efforts to identify peripheral blood biomarkers due to the diversity of lesion types and complexity of local immune responses in the lung. DA - 2015 DB - OpenUCT DO - 10.1371/journal.pone.0132249 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study TI - Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study UR - http://hdl.handle.net/11427/15315 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15315
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0132249
dc.identifier.vancouvercitationSubbian S, Tsenova L, Kim M, Wainwright HC, Visser A, Bandyopadhyay N, et al. Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study. PLoS One. 2015; http://hdl.handle.net/11427/15315.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Anatomical Pathologyen_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 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2015 Subbian et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherGranulomasen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherGene expressionen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherBlooden_ZA
dc.subject.otherLesionsen_ZA
dc.subject.otherImmune cellsen_ZA
dc.subject.otherMacrophagesen_ZA
dc.titleLesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot studyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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