Cargando…

Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by Streptococcus suis Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity

Streptococcus suis serovar 2 (S. suis serovar 2) is a zoonotic pathogen that causes meningitis in pigs and humans, and is a serious threat to the swine industry and public health. Understanding the mechanism(s) by which S. suis serovar 2 penetrates the blood–brain barrier (BBB) is crucial to elucida...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Tong, Jia, Li, Lei, Siyu, Jiang, Hexiang, Liu, Jianan, Li, Na, Langford, Paul R., Liu, Hongtao, Lei, Liancheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265368/
https://www.ncbi.nlm.nih.gov/pubmed/35805155
http://dx.doi.org/10.3390/cells11132071
_version_ 1784743196459270144
author Wu, Tong
Jia, Li
Lei, Siyu
Jiang, Hexiang
Liu, Jianan
Li, Na
Langford, Paul R.
Liu, Hongtao
Lei, Liancheng
author_facet Wu, Tong
Jia, Li
Lei, Siyu
Jiang, Hexiang
Liu, Jianan
Li, Na
Langford, Paul R.
Liu, Hongtao
Lei, Liancheng
author_sort Wu, Tong
collection PubMed
description Streptococcus suis serovar 2 (S. suis serovar 2) is a zoonotic pathogen that causes meningitis in pigs and humans, and is a serious threat to the swine industry and public health. Understanding the mechanism(s) by which S. suis serovar 2 penetrates the blood–brain barrier (BBB) is crucial to elucidating the pathogenesis of meningitis. In a previous study, we found that expression of the virulence factor enolase (Eno) by S. suis serovar 2 promotes the expression of host heat shock protein family D member 1 (HSPD1) in brain tissue, which leads to the apoptosis of porcine brain microvascular endothelial cells (PBMECs) and increased BBB permeability, which in turn promotes bacterial translocation across the BBB. However, the mechanism by which HSPD1 mediates Eno-induced apoptosis remains unclear. In this study, we demonstrate that Eno promotes the translocation of HSPD1 from mitochondria to the cytoplasm, where HSPD1 binds to β-actin (ACTB), the translocated HSPD1, and its interaction with ACTB led to adverse changes in cell morphology and promoted the expression of apoptosis-related proteins, second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3; inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP); and finally promoted cell apoptosis. These results further elucidate the role of HSPD1 in the process of Eno-induced apoptosis and increased BBB permeability, increasing our understanding of the pathogenic mechanisms of meningitis, and providing a framework for novel therapeutic strategies.
format Online
Article
Text
id pubmed-9265368
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-92653682022-07-09 Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by Streptococcus suis Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity Wu, Tong Jia, Li Lei, Siyu Jiang, Hexiang Liu, Jianan Li, Na Langford, Paul R. Liu, Hongtao Lei, Liancheng Cells Article Streptococcus suis serovar 2 (S. suis serovar 2) is a zoonotic pathogen that causes meningitis in pigs and humans, and is a serious threat to the swine industry and public health. Understanding the mechanism(s) by which S. suis serovar 2 penetrates the blood–brain barrier (BBB) is crucial to elucidating the pathogenesis of meningitis. In a previous study, we found that expression of the virulence factor enolase (Eno) by S. suis serovar 2 promotes the expression of host heat shock protein family D member 1 (HSPD1) in brain tissue, which leads to the apoptosis of porcine brain microvascular endothelial cells (PBMECs) and increased BBB permeability, which in turn promotes bacterial translocation across the BBB. However, the mechanism by which HSPD1 mediates Eno-induced apoptosis remains unclear. In this study, we demonstrate that Eno promotes the translocation of HSPD1 from mitochondria to the cytoplasm, where HSPD1 binds to β-actin (ACTB), the translocated HSPD1, and its interaction with ACTB led to adverse changes in cell morphology and promoted the expression of apoptosis-related proteins, second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3; inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP); and finally promoted cell apoptosis. These results further elucidate the role of HSPD1 in the process of Eno-induced apoptosis and increased BBB permeability, increasing our understanding of the pathogenic mechanisms of meningitis, and providing a framework for novel therapeutic strategies. MDPI 2022-06-29 /pmc/articles/PMC9265368/ /pubmed/35805155 http://dx.doi.org/10.3390/cells11132071 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
Wu, Tong
Jia, Li
Lei, Siyu
Jiang, Hexiang
Liu, Jianan
Li, Na
Langford, Paul R.
Liu, Hongtao
Lei, Liancheng
Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by Streptococcus suis Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity
title Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by Streptococcus suis Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity
title_full Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by Streptococcus suis Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity
title_fullStr Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by Streptococcus suis Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity
title_full_unstemmed Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by Streptococcus suis Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity
title_short Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by Streptococcus suis Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity
title_sort host hspd1 translocation from mitochondria to the cytoplasm induced by streptococcus suis serovar 2 enolase mediates apoptosis and loss of blood–brain barrier integrity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265368/
https://www.ncbi.nlm.nih.gov/pubmed/35805155
http://dx.doi.org/10.3390/cells11132071
work_keys_str_mv AT wutong hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity
AT jiali hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity
AT leisiyu hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity
AT jianghexiang hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity
AT liujianan hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity
AT lina hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity
AT langfordpaulr hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity
AT liuhongtao hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity
AT leiliancheng hosthspd1translocationfrommitochondriatothecytoplasminducedbystreptococcussuisserovar2enolasemediatesapoptosisandlossofbloodbrainbarrierintegrity