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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-09-01
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| Series: | PLoS Pathogens |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028333/pdf/?tool=EBI |
| _version_ | 1818337995149803520 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T15:04:04Z |
| format | Article |
| id | doaj.art-23796f7fe8214a64bb5f815a2c91b20a |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T15:04:04Z |
| publishDate | 2012-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-23796f7fe8214a64bb5f815a2c91b20a2022-12-21T23:41:04ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-09-0189e100294410.1371/journal.ppat.1002944Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.Mataleena ParikkaMilka M HammarénSanna-Kaisa E HarjulaNicholas J A HalfpennyKaisa E OksanenMarika J LahtinenElina T PajulaAntti IivanainenMarko PesuMika RämetThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028333/pdf/?tool=EBI |
| spellingShingle | 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. PLoS Pathogens |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028333/pdf/?tool=EBI |
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