Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784716722217943040
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
work_keys_str_mv AT ramonluingluceroa diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT olverayessica diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT floresgonzalezjulio diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT palaciosyadira diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT carranzaclaudia diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT aguilarduranyerany diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT vargasmarcoantonio diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT gutierrezneptali diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT medinaquerokaren diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis
AT chavezgalanleslie diversecelldeathmechanismsaresimultaneouslyactivatedinmacrophagesinfectedbyvirulentmycobacteriumtuberculosis