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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
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.
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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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