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Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses
Tuberculosis (TB) lesions are extremely complex and dynamic. Here, we review the multiple types and fates of pulmonary lesions that form following infection by Mycobacterium tuberculosis and the impact of this spatial and temporal heterogeneity on the bacteria they harbor. The diverse immunopatholog...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368385/ https://www.ncbi.nlm.nih.gov/pubmed/25703567 http://dx.doi.org/10.1111/imr.12252 |
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author | Lenaerts, Anne Barry, Clifton E Dartois, Véronique |
author_facet | Lenaerts, Anne Barry, Clifton E Dartois, Véronique |
author_sort | Lenaerts, Anne |
collection | PubMed |
description | Tuberculosis (TB) lesions are extremely complex and dynamic. Here, we review the multiple types and fates of pulmonary lesions that form following infection by Mycobacterium tuberculosis and the impact of this spatial and temporal heterogeneity on the bacteria they harbor. The diverse immunopathology of granulomas and cavities generates a plethora of microenvironments to which M. tuberculosis bacilli must adapt. This in turn affects the replication, metabolism, and relative density of bacterial subpopulations, and consequently their respective susceptibility to chemotherapy. We outline recent developments that support a paradigm shift in our understanding of lesion progression. The simple model according to which lesions within a single individual react similarly to the systemic immune response no longer prevails. Host-pathogen interactions within lesions are a dynamic process, driven by subtle and local differences in signaling pathways, resulting in diverging trajectories of lesions within a single host. The spectrum of TB lesions is a continuum with a large overlap in the lesion types found in latently infected and active TB patients. We hope this overview will guide TB researchers in the design, choice of read-outs, and interpretation of future studies in the search for predictive biomarkers and novel therapies. |
format | Online Article Text |
id | pubmed-4368385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43683852015-03-25 Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses Lenaerts, Anne Barry, Clifton E Dartois, Véronique Immunol Rev Invited Reviews Tuberculosis (TB) lesions are extremely complex and dynamic. Here, we review the multiple types and fates of pulmonary lesions that form following infection by Mycobacterium tuberculosis and the impact of this spatial and temporal heterogeneity on the bacteria they harbor. The diverse immunopathology of granulomas and cavities generates a plethora of microenvironments to which M. tuberculosis bacilli must adapt. This in turn affects the replication, metabolism, and relative density of bacterial subpopulations, and consequently their respective susceptibility to chemotherapy. We outline recent developments that support a paradigm shift in our understanding of lesion progression. The simple model according to which lesions within a single individual react similarly to the systemic immune response no longer prevails. Host-pathogen interactions within lesions are a dynamic process, driven by subtle and local differences in signaling pathways, resulting in diverging trajectories of lesions within a single host. The spectrum of TB lesions is a continuum with a large overlap in the lesion types found in latently infected and active TB patients. We hope this overview will guide TB researchers in the design, choice of read-outs, and interpretation of future studies in the search for predictive biomarkers and novel therapies. BlackWell Publishing Ltd 2015-03 2015-02-20 /pmc/articles/PMC4368385/ /pubmed/25703567 http://dx.doi.org/10.1111/imr.12252 Text en © 2015 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Invited Reviews Lenaerts, Anne Barry, Clifton E Dartois, Véronique Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses |
title | Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses |
title_full | Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses |
title_fullStr | Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses |
title_full_unstemmed | Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses |
title_short | Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses |
title_sort | heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses |
topic | Invited Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368385/ https://www.ncbi.nlm.nih.gov/pubmed/25703567 http://dx.doi.org/10.1111/imr.12252 |
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