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Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis

Infection with Mycobacterium tuberculosis leads to the development of tuberculosis (TB) with the formation of granulomatous lesions. Foamy macrophages (FM) are a hallmark of TB granulomas, because they provide the primary platform of M. tuberculosis proliferation and the main source of caseous necro...

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Autores principales: Seto, Shintaro, Nakamura, Hajime, Guo, Tz-Chun, Hikichi, Haruka, Wakabayashi, Keiko, Miyabayashi, Akiko, Nagata, Toshi, Hijikata, Minako, Keicho, Naoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551193/
https://www.ncbi.nlm.nih.gov/pubmed/36237431
http://dx.doi.org/10.3389/fcimb.2022.968543
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author Seto, Shintaro
Nakamura, Hajime
Guo, Tz-Chun
Hikichi, Haruka
Wakabayashi, Keiko
Miyabayashi, Akiko
Nagata, Toshi
Hijikata, Minako
Keicho, Naoto
author_facet Seto, Shintaro
Nakamura, Hajime
Guo, Tz-Chun
Hikichi, Haruka
Wakabayashi, Keiko
Miyabayashi, Akiko
Nagata, Toshi
Hijikata, Minako
Keicho, Naoto
author_sort Seto, Shintaro
collection PubMed
description Infection with Mycobacterium tuberculosis leads to the development of tuberculosis (TB) with the formation of granulomatous lesions. Foamy macrophages (FM) are a hallmark of TB granulomas, because they provide the primary platform of M. tuberculosis proliferation and the main source of caseous necrosis. In this study, we applied spatial multiomic profiling to identify the signatures of FM within the necrotic granulomas developed in a mouse model resembling human TB histopathology. C3HeB/FeJ mice were infected with M. tuberculosis to induce the formation of necrotic granulomas in the lungs. Using laser microdissection, necrotic granulomas were fractionated into three distinct regions, including the central caseous necrosis, the rim containing FM, and the peripheral layer of macrophages and lymphocytes, and subjected to proteomic and transcriptomic analyses. Comparison of proteomic and transcriptomic analyses of three distinct granulomatous regions revealed that four proteins/genes are commonly enriched in the rim region. Immunohistochemistry confirmed the localization of identified signatures to the rim of necrotic granulomas. We also investigated the localization of the representative markers for M1 macrophages in granulomas because the signatures of the rim included M2 macrophage markers. The localization of both macrophage markers suggests that FM in necrotic granulomas possessed the features of M1 or M2 macrophages. Gene set enrichment analysis of transcriptomic profiling revealed the upregulation of genes related to M2 macrophage activation and mTORC1 signaling in the rim. These results will provide new insights into the process of FM biogenesis, leading to further understanding of the pathophysiology of TB granulomas.
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spelling pubmed-95511932022-10-12 Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis Seto, Shintaro Nakamura, Hajime Guo, Tz-Chun Hikichi, Haruka Wakabayashi, Keiko Miyabayashi, Akiko Nagata, Toshi Hijikata, Minako Keicho, Naoto Front Cell Infect Microbiol Cellular and Infection Microbiology Infection with Mycobacterium tuberculosis leads to the development of tuberculosis (TB) with the formation of granulomatous lesions. Foamy macrophages (FM) are a hallmark of TB granulomas, because they provide the primary platform of M. tuberculosis proliferation and the main source of caseous necrosis. In this study, we applied spatial multiomic profiling to identify the signatures of FM within the necrotic granulomas developed in a mouse model resembling human TB histopathology. C3HeB/FeJ mice were infected with M. tuberculosis to induce the formation of necrotic granulomas in the lungs. Using laser microdissection, necrotic granulomas were fractionated into three distinct regions, including the central caseous necrosis, the rim containing FM, and the peripheral layer of macrophages and lymphocytes, and subjected to proteomic and transcriptomic analyses. Comparison of proteomic and transcriptomic analyses of three distinct granulomatous regions revealed that four proteins/genes are commonly enriched in the rim region. Immunohistochemistry confirmed the localization of identified signatures to the rim of necrotic granulomas. We also investigated the localization of the representative markers for M1 macrophages in granulomas because the signatures of the rim included M2 macrophage markers. The localization of both macrophage markers suggests that FM in necrotic granulomas possessed the features of M1 or M2 macrophages. Gene set enrichment analysis of transcriptomic profiling revealed the upregulation of genes related to M2 macrophage activation and mTORC1 signaling in the rim. These results will provide new insights into the process of FM biogenesis, leading to further understanding of the pathophysiology of TB granulomas. Frontiers Media S.A. 2022-09-27 /pmc/articles/PMC9551193/ /pubmed/36237431 http://dx.doi.org/10.3389/fcimb.2022.968543 Text en Copyright © 2022 Seto, Nakamura, Guo, Hikichi, Wakabayashi, Miyabayashi, Nagata, Hijikata and Keicho 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 Cellular and Infection Microbiology
Seto, Shintaro
Nakamura, Hajime
Guo, Tz-Chun
Hikichi, Haruka
Wakabayashi, Keiko
Miyabayashi, Akiko
Nagata, Toshi
Hijikata, Minako
Keicho, Naoto
Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis
title Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis
title_full Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis
title_fullStr Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis
title_full_unstemmed Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis
title_short Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis
title_sort spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of c3heb/fej mice infected with mycobacterium tuberculosis
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551193/
https://www.ncbi.nlm.nih.gov/pubmed/36237431
http://dx.doi.org/10.3389/fcimb.2022.968543
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