Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.

The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experiment...

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Autores principales:	Mataleena Parikka, Milka M Hammarén, Sanna-Kaisa E Harjula, Nicholas J A Halfpenny, Kaisa E Oksanen, Marika J Lahtinen, Elina T Pajula, Antti Iivanainen, Marko Pesu, Mika Rämet
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/23796f7fe8214a64bb5f815a2c91b20a
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spelling	oai:doaj.org-article:23796f7fe8214a64bb5f815a2c91b20a2021-11-18T06:03:55ZMycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.1553-73661553-737410.1371/journal.ppat.1002944https://doaj.org/article/23796f7fe8214a64bb5f815a2c91b20a2012-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028333/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experimental intraperitoneal infection with a low dose (≈ 35 bacteria) of Mycobacterium marinum, results in the development of a latent disease in most individuals. The infection is characterized by limited mortality (25%), stable bacterial loads 4 weeks following infection and constant numbers of highly organized granulomas in few target organs. The majority of bacteria are dormant during a latent mycobacterial infection in zebrafish, and can be activated by resuscitation promoting factor ex vivo. In 5-10% of tuberculosis cases in humans, the disease is reactivated usually as a consequence of immune suppression. In our model, we are able to show that reactivation can be efficiently induced in infected zebrafish by γ-irradiation that transiently depletes granulo/monocyte and lymphocyte pools, as determined by flow cytometry. This immunosuppression causes reactivation of the dormant mycobacterial population and a rapid outgrowth of bacteria, leading to 88% mortality in four weeks. In this study, the adult zebrafish presents itself as a unique non-mammalian vertebrate model for studying the development of latency, regulation of mycobacterial dormancy, as well as reactivation of latent or subclinical tuberculosis. The possibilities for screening for host and pathogen factors affecting the disease progression, and identifying novel therapeutic agents and vaccine targets make this established model especially attractive.Mataleena ParikkaMilka M HammarénSanna-Kaisa E HarjulaNicholas J A HalfpennyKaisa E OksanenMarika J LahtinenElina T PajulaAntti IivanainenMarko PesuMika RämetPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 9, p e1002944 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Mataleena Parikka Milka M Hammarén Sanna-Kaisa E Harjula Nicholas J A Halfpenny Kaisa E Oksanen Marika J Lahtinen Elina T Pajula Antti Iivanainen Marko Pesu Mika Rämet Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.
description	The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experimental intraperitoneal infection with a low dose (≈ 35 bacteria) of Mycobacterium marinum, results in the development of a latent disease in most individuals. The infection is characterized by limited mortality (25%), stable bacterial loads 4 weeks following infection and constant numbers of highly organized granulomas in few target organs. The majority of bacteria are dormant during a latent mycobacterial infection in zebrafish, and can be activated by resuscitation promoting factor ex vivo. In 5-10% of tuberculosis cases in humans, the disease is reactivated usually as a consequence of immune suppression. In our model, we are able to show that reactivation can be efficiently induced in infected zebrafish by γ-irradiation that transiently depletes granulo/monocyte and lymphocyte pools, as determined by flow cytometry. This immunosuppression causes reactivation of the dormant mycobacterial population and a rapid outgrowth of bacteria, leading to 88% mortality in four weeks. In this study, the adult zebrafish presents itself as a unique non-mammalian vertebrate model for studying the development of latency, regulation of mycobacterial dormancy, as well as reactivation of latent or subclinical tuberculosis. The possibilities for screening for host and pathogen factors affecting the disease progression, and identifying novel therapeutic agents and vaccine targets make this established model especially attractive.
format	article
author	Mataleena Parikka Milka M Hammarén Sanna-Kaisa E Harjula Nicholas J A Halfpenny Kaisa E Oksanen Marika J Lahtinen Elina T Pajula Antti Iivanainen Marko Pesu Mika Rämet
author_facet	Mataleena Parikka Milka M Hammarén Sanna-Kaisa E Harjula Nicholas J A Halfpenny Kaisa E Oksanen Marika J Lahtinen Elina T Pajula Antti Iivanainen Marko Pesu Mika Rämet
author_sort	Mataleena Parikka
title	Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.
title_short	Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.
title_full	Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.
title_fullStr	Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.
title_full_unstemmed	Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.
title_sort	mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/23796f7fe8214a64bb5f815a2c91b20a
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Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.

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