Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells
A hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we use...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/22028 |
| _version_ | 1829096896913735680 |
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| author | Deeqa Mahamed Mikael Boulle Yashica Ganga Chanelle Mc Arthur Steven Skroch Lance Oom Oana Catinas Kelly Pillay Myshnee Naicker Sanisha Rampersad Colisile Mathonsi Jessica Hunter Emily B Wong Moosa Suleman Gopalkrishna Sreejit Alexander S Pym Gila Lustig Alex Sigal |
| author_facet | Deeqa Mahamed Mikael Boulle Yashica Ganga Chanelle Mc Arthur Steven Skroch Lance Oom Oana Catinas Kelly Pillay Myshnee Naicker Sanisha Rampersad Colisile Mathonsi Jessica Hunter Emily B Wong Moosa Suleman Gopalkrishna Sreejit Alexander S Pym Gila Lustig Alex Sigal |
| author_sort | Deeqa Mahamed |
| collection | DOAJ |
| description | A hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we used live cell imaging to track Mtb infection outcomes in individual primary human macrophages. Internalization of Mtb aggregates caused macrophage death, and phagocytosis of large aggregates was more cytotoxic than multiple small aggregates containing similar numbers of bacilli. Macrophage death did not result in clearance of Mtb. Rather, it led to accelerated intracellular Mtb growth regardless of prior activation or macrophage type. In contrast, bacillary replication was controlled in live phagocytes. Mtb grew as a clump in dead cells, and macrophages which internalized dead infected cells were very likely to die themselves, leading to a cell death cascade. This demonstrates how pathogen virulence can be achieved through numbers and aggregation states. |
| first_indexed | 2024-04-11T09:05:06Z |
| format | Article |
| id | doaj.art-91ed3710575d48488a548fdbc63e7f89 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:06Z |
| publishDate | 2017-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-91ed3710575d48488a548fdbc63e7f892022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2017-01-01610.7554/eLife.22028Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cellsDeeqa Mahamed0Mikael Boulle1Yashica Ganga2Chanelle Mc Arthur3Steven Skroch4Lance Oom5Oana Catinas6Kelly Pillay7Myshnee Naicker8Sanisha Rampersad9Colisile Mathonsi10Jessica Hunter11Emily B Wong12Moosa Suleman13Gopalkrishna Sreejit14Alexander S Pym15Gila Lustig16Alex Sigal17https://orcid.org/0000-0001-8571-2004KwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South Africa; Max Planck Institute for Infection Biology, Berlin, GermanyKwaZulu-Natal Research Institute for TB-HIV, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; Division of Infectious Diseases, Massachusetts General Hospital, Boston, United StatesDepartment of Pulmonology and Critical Care, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Department of Pulmonology, Inkosi Albert Luthuli Central Hospital, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South AfricaKwaZulu-Natal Research Institute for TB-HIV, Durban, South Africa; University of KwaZulu-Natal, Durban, South Africa; Max Planck Institute for Infection Biology, Berlin, GermanyA hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we used live cell imaging to track Mtb infection outcomes in individual primary human macrophages. Internalization of Mtb aggregates caused macrophage death, and phagocytosis of large aggregates was more cytotoxic than multiple small aggregates containing similar numbers of bacilli. Macrophage death did not result in clearance of Mtb. Rather, it led to accelerated intracellular Mtb growth regardless of prior activation or macrophage type. In contrast, bacillary replication was controlled in live phagocytes. Mtb grew as a clump in dead cells, and macrophages which internalized dead infected cells were very likely to die themselves, leading to a cell death cascade. This demonstrates how pathogen virulence can be achieved through numbers and aggregation states.https://elifesciences.org/articles/22028Mycobacterium tuberculosishuman macrophageslive cell imaginginfection dynamicsnecrosis |
| spellingShingle | Deeqa Mahamed Mikael Boulle Yashica Ganga Chanelle Mc Arthur Steven Skroch Lance Oom Oana Catinas Kelly Pillay Myshnee Naicker Sanisha Rampersad Colisile Mathonsi Jessica Hunter Emily B Wong Moosa Suleman Gopalkrishna Sreejit Alexander S Pym Gila Lustig Alex Sigal Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells eLife Mycobacterium tuberculosis human macrophages live cell imaging infection dynamics necrosis |
| title | Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells |
| title_full | Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells |
| title_fullStr | Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells |
| title_full_unstemmed | Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells |
| title_short | Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells |
| title_sort | intracellular growth of mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells |
| topic | Mycobacterium tuberculosis human macrophages live cell imaging infection dynamics necrosis |
| url | https://elifesciences.org/articles/22028 |
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