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Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis
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 Mycobacterium tuberculosis (M. tb) can simultaneous...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147088/ https://www.ncbi.nlm.nih.gov/pubmed/35631013 http://dx.doi.org/10.3390/pathogens11050492 |
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author | Ramon-Luing, Lucero A. Olvera, Yessica Flores-Gonzalez, Julio Palacios, Yadira Carranza, Claudia Aguilar-Duran, Yerany Vargas, Marco Antonio Gutierrez, Neptali Medina-Quero, Karen Chavez-Galan, Leslie |
author_facet | Ramon-Luing, Lucero A. Olvera, Yessica Flores-Gonzalez, Julio Palacios, Yadira Carranza, Claudia Aguilar-Duran, Yerany Vargas, Marco Antonio Gutierrez, Neptali Medina-Quero, Karen Chavez-Galan, Leslie |
author_sort | Ramon-Luing, Lucero A. |
collection | PubMed |
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 Mycobacterium tuberculosis (M. tb) 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 BAX 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 RIPK3 at the transcriptional level. In addition, NLRP3 and CASP1 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 M. tb 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. |
format | Online Article Text |
id | pubmed-9147088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91470882022-05-29 Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis Ramon-Luing, Lucero A. Olvera, Yessica Flores-Gonzalez, Julio Palacios, Yadira Carranza, Claudia Aguilar-Duran, Yerany Vargas, Marco Antonio Gutierrez, Neptali Medina-Quero, Karen Chavez-Galan, Leslie Pathogens Article 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 Mycobacterium tuberculosis (M. tb) 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 BAX 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 RIPK3 at the transcriptional level. In addition, NLRP3 and CASP1 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 M. tb 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. MDPI 2022-04-21 /pmc/articles/PMC9147088/ /pubmed/35631013 http://dx.doi.org/10.3390/pathogens11050492 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ramon-Luing, Lucero A. Olvera, Yessica Flores-Gonzalez, Julio Palacios, Yadira Carranza, Claudia Aguilar-Duran, Yerany Vargas, Marco Antonio Gutierrez, Neptali Medina-Quero, Karen Chavez-Galan, Leslie Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis |
title | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis |
title_full | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis |
title_fullStr | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis |
title_full_unstemmed | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis |
title_short | Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis |
title_sort | diverse cell death mechanisms are simultaneously activated in macrophages infected by virulent mycobacterium tuberculosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147088/ https://www.ncbi.nlm.nih.gov/pubmed/35631013 http://dx.doi.org/10.3390/pathogens11050492 |
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