Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.

<h4>Background</h4>Apoptosis is thought to play a role in host defenses against intracellular pathogens, including Mycobacterium tuberculosis (Mtb), by preventing the release of intracellular components and the spread of mycobacterial infection. This study aims to investigate the role of...

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Autores principales:	Yun-Ji Lim, Ji-Ae Choi, Hong-Hee Choi, Soo-Na Cho, Hwa-Jung Kim, Eun-Kyeong Jo, Jeong-Kyu Park, Chang-Hwa Song
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3556969eb3cb48f3b821bf5d54ccddde
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spelling	oai:doaj.org-article:3556969eb3cb48f3b821bf5d54ccddde2021-11-18T07:32:20ZEndoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.1932-620310.1371/journal.pone.0028531https://doaj.org/article/3556969eb3cb48f3b821bf5d54ccddde2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22194844/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Apoptosis is thought to play a role in host defenses against intracellular pathogens, including Mycobacterium tuberculosis (Mtb), by preventing the release of intracellular components and the spread of mycobacterial infection. This study aims to investigate the role of endoplasmic reticulum (ER) stress mediated apoptosis in mycobacteria infected macrophages.<h4>Methodology/principal findings</h4>Here, we demonstrate that ER stress-induced apoptosis is associated with Mtb H37Rv-induced cell death of Raw264.7 murine macrophages. We have shown that Mtb H37Rv induced apoptosis are involved in activation of caspase-12, which resides on the cytoplasmic district of the ER. Mtb infection increase levels of other ER stress indicators in a time-dependent manner. Phosphorylation of eIF2α was decreased gradually after Mtb H37Rv infection signifying that Mtb H37Rv infection may affect eIF2α phosphorylation in an attempt to survive within macrophages. Interestingly, the survival of mycobacteria in macrophages was enhanced by silencing CHOP expression. In contrast, survival rate of mycobacteria was reduced by phosphorylation of the eIF2α. Futhermore, the levels of ROS, NO or CHOP expression were significantly increased by live Mtb H37Rv compared to heat-killed Mtb H37Rv indicating that live Mtb H37Rv could induce ER stress response.<h4>Conclusion/significance</h4>These findings indicate that eIF2α/CHOP pathway may influence intracellular survival of Mtb H37Rv in macrophages and only live Mtb H37Rv can induce ER stress response. The data support the ER stress pathway plays an important role in the pathogenesis and persistence of mycobacteria.Yun-Ji LimJi-Ae ChoiHong-Hee ChoiSoo-Na ChoHwa-Jung KimEun-Kyeong JoJeong-Kyu ParkChang-Hwa SongPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28531 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yun-Ji Lim Ji-Ae Choi Hong-Hee Choi Soo-Na Cho Hwa-Jung Kim Eun-Kyeong Jo Jeong-Kyu Park Chang-Hwa Song Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.
description	<h4>Background</h4>Apoptosis is thought to play a role in host defenses against intracellular pathogens, including Mycobacterium tuberculosis (Mtb), by preventing the release of intracellular components and the spread of mycobacterial infection. This study aims to investigate the role of endoplasmic reticulum (ER) stress mediated apoptosis in mycobacteria infected macrophages.<h4>Methodology/principal findings</h4>Here, we demonstrate that ER stress-induced apoptosis is associated with Mtb H37Rv-induced cell death of Raw264.7 murine macrophages. We have shown that Mtb H37Rv induced apoptosis are involved in activation of caspase-12, which resides on the cytoplasmic district of the ER. Mtb infection increase levels of other ER stress indicators in a time-dependent manner. Phosphorylation of eIF2α was decreased gradually after Mtb H37Rv infection signifying that Mtb H37Rv infection may affect eIF2α phosphorylation in an attempt to survive within macrophages. Interestingly, the survival of mycobacteria in macrophages was enhanced by silencing CHOP expression. In contrast, survival rate of mycobacteria was reduced by phosphorylation of the eIF2α. Futhermore, the levels of ROS, NO or CHOP expression were significantly increased by live Mtb H37Rv compared to heat-killed Mtb H37Rv indicating that live Mtb H37Rv could induce ER stress response.<h4>Conclusion/significance</h4>These findings indicate that eIF2α/CHOP pathway may influence intracellular survival of Mtb H37Rv in macrophages and only live Mtb H37Rv can induce ER stress response. The data support the ER stress pathway plays an important role in the pathogenesis and persistence of mycobacteria.
format	article
author	Yun-Ji Lim Ji-Ae Choi Hong-Hee Choi Soo-Na Cho Hwa-Jung Kim Eun-Kyeong Jo Jeong-Kyu Park Chang-Hwa Song
author_facet	Yun-Ji Lim Ji-Ae Choi Hong-Hee Choi Soo-Na Cho Hwa-Jung Kim Eun-Kyeong Jo Jeong-Kyu Park Chang-Hwa Song
author_sort	Yun-Ji Lim
title	Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.
title_short	Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.
title_full	Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.
title_fullStr	Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.
title_full_unstemmed	Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.
title_sort	endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of mycobacterium tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3556969eb3cb48f3b821bf5d54ccddde
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Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.

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