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Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis
The hallmark of tuberculosis (TB) is the formation of immune cell-enriched aggregates called granulomas. While granulomas are pathologically diverse, their tissue-wide heterogeneity has not been spatially resolved at the single-cell level in human tissues. By spatially mapping individual immune cell...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035589/ https://www.ncbi.nlm.nih.gov/pubmed/36920308 http://dx.doi.org/10.1084/jem.20221392 |
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author | Sawyer, Andrew J. Patrick, Ellis Edwards, Jarem Wilmott, James S. Fielder, Timothy Yang, Qianting Barber, Daniel L. Ernst, Joel D. Britton, Warwick J. Palendira, Umaimainthan Chen, Xinchun Feng, Carl G. |
author_facet | Sawyer, Andrew J. Patrick, Ellis Edwards, Jarem Wilmott, James S. Fielder, Timothy Yang, Qianting Barber, Daniel L. Ernst, Joel D. Britton, Warwick J. Palendira, Umaimainthan Chen, Xinchun Feng, Carl G. |
author_sort | Sawyer, Andrew J. |
collection | PubMed |
description | The hallmark of tuberculosis (TB) is the formation of immune cell-enriched aggregates called granulomas. While granulomas are pathologically diverse, their tissue-wide heterogeneity has not been spatially resolved at the single-cell level in human tissues. By spatially mapping individual immune cells in every lesion across entire tissue sections, we report that in addition to necrotizing granulomas, the human TB lung contains abundant non-necrotizing leukocyte aggregates surrounding areas of necrotizing tissue. These cellular lesions were more diverse in composition than necrotizing lesions and could be stratified into four general classes based on cellular composition and spatial distribution of B cells and macrophages. The cellular composition of non-necrotizing structures also correlates with their proximity to necrotizing lesions, indicating these are foci of distinct immune reactions adjacent to necrotizing granulomas. Together, we show that during TB, diseased lung tissue develops a histopathological superstructure comprising at least four different types of non-necrotizing cellular aggregates organized as satellites of necrotizing granulomas. |
format | Online Article Text |
id | pubmed-10035589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-100355892023-09-15 Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis Sawyer, Andrew J. Patrick, Ellis Edwards, Jarem Wilmott, James S. Fielder, Timothy Yang, Qianting Barber, Daniel L. Ernst, Joel D. Britton, Warwick J. Palendira, Umaimainthan Chen, Xinchun Feng, Carl G. J Exp Med Technical Advances and Resources The hallmark of tuberculosis (TB) is the formation of immune cell-enriched aggregates called granulomas. While granulomas are pathologically diverse, their tissue-wide heterogeneity has not been spatially resolved at the single-cell level in human tissues. By spatially mapping individual immune cells in every lesion across entire tissue sections, we report that in addition to necrotizing granulomas, the human TB lung contains abundant non-necrotizing leukocyte aggregates surrounding areas of necrotizing tissue. These cellular lesions were more diverse in composition than necrotizing lesions and could be stratified into four general classes based on cellular composition and spatial distribution of B cells and macrophages. The cellular composition of non-necrotizing structures also correlates with their proximity to necrotizing lesions, indicating these are foci of distinct immune reactions adjacent to necrotizing granulomas. Together, we show that during TB, diseased lung tissue develops a histopathological superstructure comprising at least four different types of non-necrotizing cellular aggregates organized as satellites of necrotizing granulomas. Rockefeller University Press 2023-03-15 /pmc/articles/PMC10035589/ /pubmed/36920308 http://dx.doi.org/10.1084/jem.20221392 Text en © 2023 Sawyer et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Technical Advances and Resources Sawyer, Andrew J. Patrick, Ellis Edwards, Jarem Wilmott, James S. Fielder, Timothy Yang, Qianting Barber, Daniel L. Ernst, Joel D. Britton, Warwick J. Palendira, Umaimainthan Chen, Xinchun Feng, Carl G. Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis |
title | Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis |
title_full | Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis |
title_fullStr | Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis |
title_full_unstemmed | Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis |
title_short | Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis |
title_sort | spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis |
topic | Technical Advances and Resources |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035589/ https://www.ncbi.nlm.nih.gov/pubmed/36920308 http://dx.doi.org/10.1084/jem.20221392 |
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