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Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study

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,...

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Autores principales: Subbian, Selvakumar, Tsenova, Liana, Kim, Mi-Jeong, Wainwright, Helen C., Visser, Annalie, Bandyopadhyay, Nirmalya, Bader, Joel S., Karakousis, Petros C., Murrmann, Gabriele B., Bekker, Linda-Gail, Russell, David G., Kaplan, Gilla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489805/
https://www.ncbi.nlm.nih.gov/pubmed/26133981
http://dx.doi.org/10.1371/journal.pone.0132249
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author Subbian, Selvakumar
Tsenova, Liana
Kim, Mi-Jeong
Wainwright, Helen C.
Visser, Annalie
Bandyopadhyay, Nirmalya
Bader, Joel S.
Karakousis, Petros C.
Murrmann, Gabriele B.
Bekker, Linda-Gail
Russell, David G.
Kaplan, Gilla
author_facet Subbian, Selvakumar
Tsenova, Liana
Kim, Mi-Jeong
Wainwright, Helen C.
Visser, Annalie
Bandyopadhyay, Nirmalya
Bader, Joel S.
Karakousis, Petros C.
Murrmann, Gabriele B.
Bekker, Linda-Gail
Russell, David G.
Kaplan, Gilla
author_sort Subbian, Selvakumar
collection PubMed
description 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.
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spelling pubmed-44898052015-07-15 Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study Subbian, Selvakumar Tsenova, Liana Kim, Mi-Jeong Wainwright, Helen C. Visser, Annalie Bandyopadhyay, Nirmalya Bader, Joel S. Karakousis, Petros C. Murrmann, Gabriele B. Bekker, Linda-Gail Russell, David G. Kaplan, Gilla PLoS One Research Article 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. Public Library of Science 2015-07-02 /pmc/articles/PMC4489805/ /pubmed/26133981 http://dx.doi.org/10.1371/journal.pone.0132249 Text en © 2015 Subbian et al http://creativecommons.org/licenses/by/4.0/ This 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 properly credited.
spellingShingle Research Article
Subbian, Selvakumar
Tsenova, Liana
Kim, Mi-Jeong
Wainwright, Helen C.
Visser, Annalie
Bandyopadhyay, Nirmalya
Bader, Joel S.
Karakousis, Petros C.
Murrmann, Gabriele B.
Bekker, Linda-Gail
Russell, David G.
Kaplan, Gilla
Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study
title Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study
title_full Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study
title_fullStr Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study
title_full_unstemmed Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study
title_short Lesion-Specific Immune Response in Granulomas of Patients with Pulmonary Tuberculosis: A Pilot Study
title_sort lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: a pilot study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489805/
https://www.ncbi.nlm.nih.gov/pubmed/26133981
http://dx.doi.org/10.1371/journal.pone.0132249
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