Cargando…

Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion

Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show th...

Descripción completa

Detalles Bibliográficos
Autores principales: Zou, Song-Song, Zou, Qing-Cui, Xiong, Wen-Jing, Cui, Ning-Yi, Wang, Ke, Liu, Hao-Xuan, Lou, Wen-Juan, Higazy, Doaa, Zhang, Ya-Ge, Cui, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439198/
https://www.ncbi.nlm.nih.gov/pubmed/34532298
http://dx.doi.org/10.3389/fcimb.2021.701820
_version_ 1783752488647655424
author Zou, Song-Song
Zou, Qing-Cui
Xiong, Wen-Jing
Cui, Ning-Yi
Wang, Ke
Liu, Hao-Xuan
Lou, Wen-Juan
Higazy, Doaa
Zhang, Ya-Ge
Cui, Min
author_facet Zou, Song-Song
Zou, Qing-Cui
Xiong, Wen-Jing
Cui, Ning-Yi
Wang, Ke
Liu, Hao-Xuan
Lou, Wen-Juan
Higazy, Doaa
Zhang, Ya-Ge
Cui, Min
author_sort Zou, Song-Song
collection PubMed
description Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show that extracellular HMGB1 facilitates immune cell transmigration. Furthermore, the migration of immune cells into the CNS dramatically increases during JEV infection which may enhance viral clearance, but paradoxically expedite the onset of Japanese encephalitis (JE). In this study, brain microvascular endothelial cells (BMECs) were utilized for the detection of HMGB1 release, and leucocyte, adhesion, and the integrity of the BBB in vitro. Genetically modified JEV-expressing EGFP (EGFP-JEV) and the BBB model were established to trace JEV-infected immune cell transmigration, which mimics the process of viral neuroinfection. We find that JEV causes HMGB1 release from BMECs while increasing adhesion molecules. Recombinant HMGB1 enhances leukocyte-endothelium adhesion, facilitating JEV-infected monocyte transmigration across endothelia. Thus, JEV successfully utilizes infected monocytes to spread into the brain, expanding inside of the brain, and leading to the acceleration of JE onset, which was facilitated by HMGB1. HMGB1-promoted monocyte transmigration may represent the mechanism of JEV neuroinvasion, revealing potential therapeutic targets.
format Online
Article
Text
id pubmed-8439198
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-84391982021-09-15 Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion Zou, Song-Song Zou, Qing-Cui Xiong, Wen-Jing Cui, Ning-Yi Wang, Ke Liu, Hao-Xuan Lou, Wen-Juan Higazy, Doaa Zhang, Ya-Ge Cui, Min Front Cell Infect Microbiol Cellular and Infection Microbiology Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show that extracellular HMGB1 facilitates immune cell transmigration. Furthermore, the migration of immune cells into the CNS dramatically increases during JEV infection which may enhance viral clearance, but paradoxically expedite the onset of Japanese encephalitis (JE). In this study, brain microvascular endothelial cells (BMECs) were utilized for the detection of HMGB1 release, and leucocyte, adhesion, and the integrity of the BBB in vitro. Genetically modified JEV-expressing EGFP (EGFP-JEV) and the BBB model were established to trace JEV-infected immune cell transmigration, which mimics the process of viral neuroinfection. We find that JEV causes HMGB1 release from BMECs while increasing adhesion molecules. Recombinant HMGB1 enhances leukocyte-endothelium adhesion, facilitating JEV-infected monocyte transmigration across endothelia. Thus, JEV successfully utilizes infected monocytes to spread into the brain, expanding inside of the brain, and leading to the acceleration of JE onset, which was facilitated by HMGB1. HMGB1-promoted monocyte transmigration may represent the mechanism of JEV neuroinvasion, revealing potential therapeutic targets. Frontiers Media S.A. 2021-08-31 /pmc/articles/PMC8439198/ /pubmed/34532298 http://dx.doi.org/10.3389/fcimb.2021.701820 Text en Copyright © 2021 Zou, Zou, Xiong, Cui, Wang, Liu, Lou, Higazy, Zhang and Cui https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Zou, Song-Song
Zou, Qing-Cui
Xiong, Wen-Jing
Cui, Ning-Yi
Wang, Ke
Liu, Hao-Xuan
Lou, Wen-Juan
Higazy, Doaa
Zhang, Ya-Ge
Cui, Min
Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_full Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_fullStr Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_full_unstemmed Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_short Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion
title_sort brain microvascular endothelial cell-derived hmgb1 facilitates monocyte adhesion and transmigration to promote jev neuroinvasion
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439198/
https://www.ncbi.nlm.nih.gov/pubmed/34532298
http://dx.doi.org/10.3389/fcimb.2021.701820
work_keys_str_mv AT zousongsong brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT zouqingcui brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT xiongwenjing brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT cuiningyi brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT wangke brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT liuhaoxuan brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT louwenjuan brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT higazydoaa brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT zhangyage brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion
AT cuimin brainmicrovascularendothelialcellderivedhmgb1facilitatesmonocyteadhesionandtransmigrationtopromotejevneuroinvasion