Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia

Abstract Neurologic melioidosis occurs in both human and animals; however, the mechanism by which the pathogen Burkholderia pseudomallei invades the central nervous system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been suggested as a putative portal; however, during melioidosis,...

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Autores principales:	Pei-Tan Hsueh, Hsi-Hsun Lin, Chiu-Lin Liu, Wei-Fen Ni, Ya-Lei Chen, Yao-Shen Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Pseudomallei Brain-infiltrating Leukocytes (BILs) Endotoxemic Mice Cerebral Cytokine Endotoxemia Group Medicine R Science Q
Acceso en línea:	https://doaj.org/article/699435dfb7ed4321aefe5e745744d14b
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spelling	oai:doaj.org-article:699435dfb7ed4321aefe5e745744d14b2021-12-02T15:09:06ZBurkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia10.1038/s41598-018-31778-82045-2322https://doaj.org/article/699435dfb7ed4321aefe5e745744d14b2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31778-8https://doaj.org/toc/2045-2322Abstract Neurologic melioidosis occurs in both human and animals; however, the mechanism by which the pathogen Burkholderia pseudomallei invades the central nervous system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been suggested as a putative portal; however, during melioidosis, lipopolysaccharide (LPS) can drive disruption of the blood-brain barrier (BBB). This study aims to test whether the Trojan horse-like mechanism occurs during endotoxemia. The expression levels of cerebral cytokines, chemokines and cell adhesion molecules; the activation of astrocytes, microglia and endothelial cells; and the increased vascular permeability and brain-infiltrating leukocytes were evaluated using B. pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans LPS-induced brains. Accordingly, different degrees of BBB damage in those brains with endotoxemia were established. The B. multivorans LPS-induced brain exhibited the highest levels of disruptive BBB according to the above mediators/indicators. Into these distinct groups of endotoxemic mice, B. pseudomallei-loaded Ly6C cells or free B. pseudomallei were adoptively transferred at equal bacterial concentrations (103 CFU). The bacterial load and number of cases of meningeal neutrophil infiltration in the brains of animals treated with B. pseudomallei-loaded Ly6C cells were higher than those in brains induced by free B. pseudomallei in any of the endotoxemic groups. In particular, these results were reproducible in B. multivorans LPS-induced brains. We suggest that B. pseudomallei-loaded cells can act as a Trojan horse and are more effective than free B. pseudomallei in invading the CNS under septic or endotoxemic conditions even when there is a high degree of BBB disruption.Pei-Tan HsuehHsi-Hsun LinChiu-Lin LiuWei-Fen NiYa-Lei ChenYao-Shen ChenNature PortfolioarticlePseudomalleiBrain-infiltrating Leukocytes (BILs)Endotoxemic MiceCerebral CytokineEndotoxemia GroupMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pseudomallei Brain-infiltrating Leukocytes (BILs) Endotoxemic Mice Cerebral Cytokine Endotoxemia Group Medicine R Science Q
spellingShingle	Pseudomallei Brain-infiltrating Leukocytes (BILs) Endotoxemic Mice Cerebral Cytokine Endotoxemia Group Medicine R Science Q Pei-Tan Hsueh Hsi-Hsun Lin Chiu-Lin Liu Wei-Fen Ni Ya-Lei Chen Yao-Shen Chen Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia
description	Abstract Neurologic melioidosis occurs in both human and animals; however, the mechanism by which the pathogen Burkholderia pseudomallei invades the central nervous system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been suggested as a putative portal; however, during melioidosis, lipopolysaccharide (LPS) can drive disruption of the blood-brain barrier (BBB). This study aims to test whether the Trojan horse-like mechanism occurs during endotoxemia. The expression levels of cerebral cytokines, chemokines and cell adhesion molecules; the activation of astrocytes, microglia and endothelial cells; and the increased vascular permeability and brain-infiltrating leukocytes were evaluated using B. pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans LPS-induced brains. Accordingly, different degrees of BBB damage in those brains with endotoxemia were established. The B. multivorans LPS-induced brain exhibited the highest levels of disruptive BBB according to the above mediators/indicators. Into these distinct groups of endotoxemic mice, B. pseudomallei-loaded Ly6C cells or free B. pseudomallei were adoptively transferred at equal bacterial concentrations (103 CFU). The bacterial load and number of cases of meningeal neutrophil infiltration in the brains of animals treated with B. pseudomallei-loaded Ly6C cells were higher than those in brains induced by free B. pseudomallei in any of the endotoxemic groups. In particular, these results were reproducible in B. multivorans LPS-induced brains. We suggest that B. pseudomallei-loaded cells can act as a Trojan horse and are more effective than free B. pseudomallei in invading the CNS under septic or endotoxemic conditions even when there is a high degree of BBB disruption.
format	article
author	Pei-Tan Hsueh Hsi-Hsun Lin Chiu-Lin Liu Wei-Fen Ni Ya-Lei Chen Yao-Shen Chen
author_facet	Pei-Tan Hsueh Hsi-Hsun Lin Chiu-Lin Liu Wei-Fen Ni Ya-Lei Chen Yao-Shen Chen
author_sort	Pei-Tan Hsueh
title	Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia
title_short	Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia
title_full	Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia
title_fullStr	Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia
title_full_unstemmed	Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia
title_sort	burkholderia pseudomallei-loaded cells act as a trojan horse to invade the brain during endotoxemia
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/699435dfb7ed4321aefe5e745744d14b
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Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia

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