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An in vitro model of Mycobacterium leprae induced granuloma formation

BACKGROUND: Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae. In the pathogenesis of leprosy, granulomas play a key role, however, the mechanisms of the formation and maintenance of M. leprae granulomas are still not clearly understood. METHODS: To be...

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Autores principales: Wang, Hongsheng, Maeda, Yumi, Fukutomi, Yasuo, Makino, Masahiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693892/
https://www.ncbi.nlm.nih.gov/pubmed/23782413
http://dx.doi.org/10.1186/1471-2334-13-279
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author Wang, Hongsheng
Maeda, Yumi
Fukutomi, Yasuo
Makino, Masahiko
author_facet Wang, Hongsheng
Maeda, Yumi
Fukutomi, Yasuo
Makino, Masahiko
author_sort Wang, Hongsheng
collection PubMed
description BACKGROUND: Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae. In the pathogenesis of leprosy, granulomas play a key role, however, the mechanisms of the formation and maintenance of M. leprae granulomas are still not clearly understood. METHODS: To better understand the molecular physiology of M. leprae granulomas and the interaction between the bacilli and human host cells, we developed an in vitro model of human granulomas, which mimicked the in vivo granulomas of leprosy. Macrophages were differentiated from human monocytes, and infected with M. leprae, and then cultured with autologous human peripheral blood mononuclear cells (PBMCs). RESULTS: Robust granuloma-like aggregates were obtained only when the M. leprae infected macrophages were co-cultured with PBMCs. Histological examination showed M. leprae within the cytoplasmic center of the multinucleated giant cells, and these bacilli were metabolically active. Macrophages of both M1 and M2 types co-existed in the granuloma like aggregates. There was a strong relationship between the formation of granulomas and changes in the expression levels of cell surface antigens on macrophages, cytokine production and the macrophage polarization. The viability of M. leprae isolated from granulomas indicated that the formation of host cell aggregates benefited the host, but the bacilli also remained metabolically active. CONCLUSIONS: A simple in vitro model of human M. leprae granulomas was established using human monocyte-derived macrophages and PBMCs. This system may be useful to unravel the mechanisms of disease progression, and subsequently develop methods to control leprosy.
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spelling pubmed-36938922013-06-27 An in vitro model of Mycobacterium leprae induced granuloma formation Wang, Hongsheng Maeda, Yumi Fukutomi, Yasuo Makino, Masahiko BMC Infect Dis Research Article BACKGROUND: Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae. In the pathogenesis of leprosy, granulomas play a key role, however, the mechanisms of the formation and maintenance of M. leprae granulomas are still not clearly understood. METHODS: To better understand the molecular physiology of M. leprae granulomas and the interaction between the bacilli and human host cells, we developed an in vitro model of human granulomas, which mimicked the in vivo granulomas of leprosy. Macrophages were differentiated from human monocytes, and infected with M. leprae, and then cultured with autologous human peripheral blood mononuclear cells (PBMCs). RESULTS: Robust granuloma-like aggregates were obtained only when the M. leprae infected macrophages were co-cultured with PBMCs. Histological examination showed M. leprae within the cytoplasmic center of the multinucleated giant cells, and these bacilli were metabolically active. Macrophages of both M1 and M2 types co-existed in the granuloma like aggregates. There was a strong relationship between the formation of granulomas and changes in the expression levels of cell surface antigens on macrophages, cytokine production and the macrophage polarization. The viability of M. leprae isolated from granulomas indicated that the formation of host cell aggregates benefited the host, but the bacilli also remained metabolically active. CONCLUSIONS: A simple in vitro model of human M. leprae granulomas was established using human monocyte-derived macrophages and PBMCs. This system may be useful to unravel the mechanisms of disease progression, and subsequently develop methods to control leprosy. BioMed Central 2013-06-20 /pmc/articles/PMC3693892/ /pubmed/23782413 http://dx.doi.org/10.1186/1471-2334-13-279 Text en Copyright © 2013 Wang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Hongsheng
Maeda, Yumi
Fukutomi, Yasuo
Makino, Masahiko
An in vitro model of Mycobacterium leprae induced granuloma formation
title An in vitro model of Mycobacterium leprae induced granuloma formation
title_full An in vitro model of Mycobacterium leprae induced granuloma formation
title_fullStr An in vitro model of Mycobacterium leprae induced granuloma formation
title_full_unstemmed An in vitro model of Mycobacterium leprae induced granuloma formation
title_short An in vitro model of Mycobacterium leprae induced granuloma formation
title_sort in vitro model of mycobacterium leprae induced granuloma formation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693892/
https://www.ncbi.nlm.nih.gov/pubmed/23782413
http://dx.doi.org/10.1186/1471-2334-13-279
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