Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent <i>Mycobacterium tuberculosis</i>
Macrophages are necessary to eliminate pathogens. However, some pathogens have developed mechanisms to avoid the immune response. One of them is modulating the cell death mechanism to favor pathogen survival. In this study, we evaluated if virulent <i>Mycobacterium tuberculosis</i> (<...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/5/492 |
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| author | Lucero A. Ramon-Luing Yessica Olvera Julio Flores-Gonzalez Yadira Palacios Claudia Carranza Yerany Aguilar-Duran Marco Antonio Vargas Neptali Gutierrez Karen Medina-Quero Leslie Chavez-Galan |
| author_facet | Lucero A. Ramon-Luing Yessica Olvera Julio Flores-Gonzalez Yadira Palacios Claudia Carranza Yerany Aguilar-Duran Marco Antonio Vargas Neptali Gutierrez Karen Medina-Quero Leslie Chavez-Galan |
| author_sort | Lucero A. Ramon-Luing |
| collection | DOAJ |
| description | Macrophages are necessary to eliminate pathogens. However, some pathogens have developed mechanisms to avoid the immune response. One of them is modulating the cell death mechanism to favor pathogen survival. In this study, we evaluated if virulent <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) can simultaneously activate more than one cell death mechanism. We infected human monocyte-derived macrophages (MDM) in vitro with avirulent (H37Ra) and virulent (H37Rv) strains, and then we measured molecules involved in apoptosis, necroptosis, and pyroptosis. Our data showed that H37Rv infection increased the BCL-2 transcript and protein, decreased the <i>BAX</i> transcript, and increased phosphorylated BCL-2 at the protein level. Moreover, H37Rv infection increased the expression of the molecules involved in the necroptotic pathway, such as ASK1, p-38, RIPK1, RIPK3, and caspase-8, while H37Ra increased caspase-8 and decreased <i>RIPK3</i> at the transcriptional level. In addition, <i>NLRP3</i> and <i>CASP1</i> expression was increased at low MOI in both strains, while IL-1β was independent of virulence but dependent on infection MOI, suggesting the activation of pyroptosis. These findings suggest that virulent <i>M. tb</i> inhibits the apoptosis mediated by BCL-2 family molecules but, at the same time, increases the expression of molecules involved in apoptosis, necroptosis, and pyroptosis at the transcriptional and protein levels, probably as a mechanism to avoid the immune response and guarantee its survival. |
| first_indexed | 2024-03-10T03:12:53Z |
| format | Article |
| id | doaj.art-f0e1f54834114b3ebdf33c4f43d8ad96 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T03:12:53Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-f0e1f54834114b3ebdf33c4f43d8ad962023-11-23T12:31:27ZengMDPI AGPathogens2076-08172022-04-0111549210.3390/pathogens11050492Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent <i>Mycobacterium tuberculosis</i>Lucero A. Ramon-Luing0Yessica Olvera1Julio Flores-Gonzalez2Yadira Palacios3Claudia Carranza4Yerany Aguilar-Duran5Marco Antonio Vargas6Neptali Gutierrez7Karen Medina-Quero8Leslie Chavez-Galan9Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoResearch Department, Military School of Graduate of Health, SEDENA, Mexico City 11200, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoLaboratory of Tuberculosis Immunobiology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoResearch Department, Military School of Graduate of Health, SEDENA, Mexico City 11200, MexicoResearch Department, Military School of Graduate of Health, SEDENA, Mexico City 11200, MexicoResearch Department, Military School of Graduate of Health, SEDENA, Mexico City 11200, MexicoLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City 14080, MexicoMacrophages are necessary to eliminate pathogens. However, some pathogens have developed mechanisms to avoid the immune response. One of them is modulating the cell death mechanism to favor pathogen survival. In this study, we evaluated if virulent <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) can simultaneously activate more than one cell death mechanism. We infected human monocyte-derived macrophages (MDM) in vitro with avirulent (H37Ra) and virulent (H37Rv) strains, and then we measured molecules involved in apoptosis, necroptosis, and pyroptosis. Our data showed that H37Rv infection increased the BCL-2 transcript and protein, decreased the <i>BAX</i> transcript, and increased phosphorylated BCL-2 at the protein level. Moreover, H37Rv infection increased the expression of the molecules involved in the necroptotic pathway, such as ASK1, p-38, RIPK1, RIPK3, and caspase-8, while H37Ra increased caspase-8 and decreased <i>RIPK3</i> at the transcriptional level. In addition, <i>NLRP3</i> and <i>CASP1</i> expression was increased at low MOI in both strains, while IL-1β was independent of virulence but dependent on infection MOI, suggesting the activation of pyroptosis. These findings suggest that virulent <i>M. tb</i> inhibits the apoptosis mediated by BCL-2 family molecules but, at the same time, increases the expression of molecules involved in apoptosis, necroptosis, and pyroptosis at the transcriptional and protein levels, probably as a mechanism to avoid the immune response and guarantee its survival.https://www.mdpi.com/2076-0817/11/5/492macrophagestuberculosisvirulenceapoptosisnecroptosispyroptosis |
| spellingShingle | Lucero A. Ramon-Luing Yessica Olvera Julio Flores-Gonzalez Yadira Palacios Claudia Carranza Yerany Aguilar-Duran Marco Antonio Vargas Neptali Gutierrez Karen Medina-Quero Leslie Chavez-Galan Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent <i>Mycobacterium tuberculosis</i> Pathogens macrophages tuberculosis virulence apoptosis necroptosis pyroptosis |
| title | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent <i>Mycobacterium tuberculosis</i> |
| title_full | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent <i>Mycobacterium tuberculosis</i> |
| title_fullStr | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent <i>Mycobacterium tuberculosis</i> |
| title_full_unstemmed | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent <i>Mycobacterium tuberculosis</i> |
| title_short | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent <i>Mycobacterium tuberculosis</i> |
| title_sort | diverse cell death mechanisms are simultaneously activated in macrophages infected by virulent i mycobacterium tuberculosis i |
| topic | macrophages tuberculosis virulence apoptosis necroptosis pyroptosis |
| url | https://www.mdpi.com/2076-0817/11/5/492 |
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