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Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs

Mycobacterium tuberculosis (Mtb) bacilli are the causative agent of tuberculosis (TB), a major killer of mankind. Although it is widely accepted that local interactions between Mtb and the immune system in the tuberculous granuloma determine whether the outcome of infection is controlled or dissemin...

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Autores principales: Magoulopoulou, Anastasia, Qian, Xiaoyan, Pediatama Setiabudiawan, Todia, Marco Salas, Sergio, Yokota, Chika, Rottenberg, Martin E., Nilsson, Mats, Carow, Berit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157500/
https://www.ncbi.nlm.nih.gov/pubmed/35663950
http://dx.doi.org/10.3389/fimmu.2022.876321
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author Magoulopoulou, Anastasia
Qian, Xiaoyan
Pediatama Setiabudiawan, Todia
Marco Salas, Sergio
Yokota, Chika
Rottenberg, Martin E.
Nilsson, Mats
Carow, Berit
author_facet Magoulopoulou, Anastasia
Qian, Xiaoyan
Pediatama Setiabudiawan, Todia
Marco Salas, Sergio
Yokota, Chika
Rottenberg, Martin E.
Nilsson, Mats
Carow, Berit
author_sort Magoulopoulou, Anastasia
collection PubMed
description Mycobacterium tuberculosis (Mtb) bacilli are the causative agent of tuberculosis (TB), a major killer of mankind. Although it is widely accepted that local interactions between Mtb and the immune system in the tuberculous granuloma determine whether the outcome of infection is controlled or disseminated, these have been poorly studied due to methodological constraints. We have recently used a spatial transcriptomic technique, in situ sequencing (ISS), to define the spatial distribution of immune transcripts in TB mouse lungs. To further contribute to the understanding of the immune microenvironments of Mtb and their local diversity, we here present two complementary automated bacteria-guided analysis pipelines. These position 33 ISS-identified immune transcripts in relation to single bacteria and bacteria clusters. The analysis was applied on new ISS data from lung sections of Mtb-infected C57BL/6 and C3HeB/FeJ mice. In lungs from C57BL/6 mice early and late post infection, transcripts that define inflammatory macrophages were enriched at subcellular distances to bacteria, indicating the activation of infected macrophages. In contrast, expression patterns associated to antigen presentation were enriched in non-infected cells at 12 weeks post infection. T-cell transcripts were evenly distributed in the tissue. In Mtb-infected C3HeB/FeJ mice, transcripts characterizing activated macrophages localized in apposition to small bacteria clusters, but not in organized granulomas. Despite differences in the susceptibility to Mtb, the transcript patterns found around small bacteria clusters of C3HeB/FeJ and C57BL/6 mice were similar. Altogether, the presented tools allow us to characterize in depth the immune cell populations and their activation that interact with Mtb in the infected lung.
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spelling pubmed-91575002022-06-02 Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs Magoulopoulou, Anastasia Qian, Xiaoyan Pediatama Setiabudiawan, Todia Marco Salas, Sergio Yokota, Chika Rottenberg, Martin E. Nilsson, Mats Carow, Berit Front Immunol Immunology Mycobacterium tuberculosis (Mtb) bacilli are the causative agent of tuberculosis (TB), a major killer of mankind. Although it is widely accepted that local interactions between Mtb and the immune system in the tuberculous granuloma determine whether the outcome of infection is controlled or disseminated, these have been poorly studied due to methodological constraints. We have recently used a spatial transcriptomic technique, in situ sequencing (ISS), to define the spatial distribution of immune transcripts in TB mouse lungs. To further contribute to the understanding of the immune microenvironments of Mtb and their local diversity, we here present two complementary automated bacteria-guided analysis pipelines. These position 33 ISS-identified immune transcripts in relation to single bacteria and bacteria clusters. The analysis was applied on new ISS data from lung sections of Mtb-infected C57BL/6 and C3HeB/FeJ mice. In lungs from C57BL/6 mice early and late post infection, transcripts that define inflammatory macrophages were enriched at subcellular distances to bacteria, indicating the activation of infected macrophages. In contrast, expression patterns associated to antigen presentation were enriched in non-infected cells at 12 weeks post infection. T-cell transcripts were evenly distributed in the tissue. In Mtb-infected C3HeB/FeJ mice, transcripts characterizing activated macrophages localized in apposition to small bacteria clusters, but not in organized granulomas. Despite differences in the susceptibility to Mtb, the transcript patterns found around small bacteria clusters of C3HeB/FeJ and C57BL/6 mice were similar. Altogether, the presented tools allow us to characterize in depth the immune cell populations and their activation that interact with Mtb in the infected lung. Frontiers Media S.A. 2022-05-18 /pmc/articles/PMC9157500/ /pubmed/35663950 http://dx.doi.org/10.3389/fimmu.2022.876321 Text en Copyright © 2022 Magoulopoulou, Qian, Pediatama Setiabudiawan, Marco Salas, Yokota, Rottenberg, Nilsson and Carow https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Magoulopoulou, Anastasia
Qian, Xiaoyan
Pediatama Setiabudiawan, Todia
Marco Salas, Sergio
Yokota, Chika
Rottenberg, Martin E.
Nilsson, Mats
Carow, Berit
Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs
title Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs
title_full Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs
title_fullStr Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs
title_full_unstemmed Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs
title_short Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs
title_sort spatial resolution of mycobacterium tuberculosis bacteria and their surrounding immune environments based on selected key transcripts in mouse lungs
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157500/
https://www.ncbi.nlm.nih.gov/pubmed/35663950
http://dx.doi.org/10.3389/fimmu.2022.876321
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