Inhibition of apoptosis by Rv2456c through nuclear factor-κB extends the survival of Mycobacterium tuberculosis
Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8+ T cells, and to be modulated by mycobacterial proteins. Since f...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2016-01-01
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| Series: | International Journal of Mycobacteriology |
| Subjects: | |
| Online Access: | http://www.ijmyco.org/article.asp?issn=2212-5531;year=2016;volume=5;issue=4;spage=426;epage=436;aulast=Smith |
| _version_ | 1828488631397908480 |
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| author | Kristen L. Jurcic Smith Sunhee Lee |
| author_facet | Kristen L. Jurcic Smith Sunhee Lee |
| author_sort | Kristen L. Jurcic Smith |
| collection | DOAJ |
| description | Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8+ T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. Tuberculosis and host cell apoptosis, we screened M. Tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID). One of these FID mutants, FID19, had a transposon insertion in Rv2456c and is important for survival in host cells. The lack of the protein resulted in enhanced caspase-3 mediated apoptosis, which is probably due to an inability to activate nuclear factor-κB. Additionally, FID19 infection enhanced polyfunctional CD8+ T cells and induced a higher frequency of interferon-γ secreting immune cells in a murine model. Taken together, our data suggest that Rv2456c is important for the survival of H37Rv by subduing the innate and ultimately adaptive immune responses of its host by preventing apoptosis of the infected cell. Better understanding of the host-mycobacterial interactions may be beneficial to develop novel drug targets and engineer more efficacious vaccine strains against tuberculosis. |
| first_indexed | 2024-12-11T10:11:25Z |
| format | Article |
| id | doaj.art-b238c0a02647417eafc07ff2da99472d |
| institution | Directory Open Access Journal |
| issn | 2212-5531 2212-554X |
| language | English |
| last_indexed | 2024-12-11T10:11:25Z |
| publishDate | 2016-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | International Journal of Mycobacteriology |
| spelling | doaj.art-b238c0a02647417eafc07ff2da99472d2022-12-22T01:11:44ZengWolters Kluwer Medknow PublicationsInternational Journal of Mycobacteriology2212-55312212-554X2016-01-015442643610.1016/j.ijmyco.2016.06.018Inhibition of apoptosis by Rv2456c through nuclear factor-κB extends the survival of Mycobacterium tuberculosisKristen L. Jurcic SmithSunhee LeeMycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8+ T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. Tuberculosis and host cell apoptosis, we screened M. Tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID). One of these FID mutants, FID19, had a transposon insertion in Rv2456c and is important for survival in host cells. The lack of the protein resulted in enhanced caspase-3 mediated apoptosis, which is probably due to an inability to activate nuclear factor-κB. Additionally, FID19 infection enhanced polyfunctional CD8+ T cells and induced a higher frequency of interferon-γ secreting immune cells in a murine model. Taken together, our data suggest that Rv2456c is important for the survival of H37Rv by subduing the innate and ultimately adaptive immune responses of its host by preventing apoptosis of the infected cell. Better understanding of the host-mycobacterial interactions may be beneficial to develop novel drug targets and engineer more efficacious vaccine strains against tuberculosis.http://www.ijmyco.org/article.asp?issn=2212-5531;year=2016;volume=5;issue=4;spage=426;epage=436;aulast=SmithApoptosisMycobacterium tuberculosisTuberculosisVaccine |
| spellingShingle | Kristen L. Jurcic Smith Sunhee Lee Inhibition of apoptosis by Rv2456c through nuclear factor-κB extends the survival of Mycobacterium tuberculosis International Journal of Mycobacteriology Apoptosis Mycobacterium tuberculosis Tuberculosis Vaccine |
| title | Inhibition of apoptosis by Rv2456c through nuclear factor-κB extends the survival of Mycobacterium tuberculosis |
| title_full | Inhibition of apoptosis by Rv2456c through nuclear factor-κB extends the survival of Mycobacterium tuberculosis |
| title_fullStr | Inhibition of apoptosis by Rv2456c through nuclear factor-κB extends the survival of Mycobacterium tuberculosis |
| title_full_unstemmed | Inhibition of apoptosis by Rv2456c through nuclear factor-κB extends the survival of Mycobacterium tuberculosis |
| title_short | Inhibition of apoptosis by Rv2456c through nuclear factor-κB extends the survival of Mycobacterium tuberculosis |
| title_sort | inhibition of apoptosis by rv2456c through nuclear factor κb extends the survival of mycobacterium tuberculosis |
| topic | Apoptosis Mycobacterium tuberculosis Tuberculosis Vaccine |
| url | http://www.ijmyco.org/article.asp?issn=2212-5531;year=2016;volume=5;issue=4;spage=426;epage=436;aulast=Smith |
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