Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration

Autores
Peralta Ramos, Javier María; Iribarren, Pablo; Bousset, Luc; Melki, Ronald; Baekelandt, Veerle; Van der Perren, Anke
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Innate immune activation and chronic neuroinflammation are characteristic features of many neurodegenerative diseases including Parkinson´s disease (PD) and may contribute to the pathophysiology of the disease. The discovery of misfolded alpha-synuclein (αSYN) protein aggregates, which amplify in a ?prion-like? fashion, has led us to consider that pathogenic αSYN might be hijacking the activation and mobilization mechanism of the peripheral immune system to reach and disseminate within the CNS. Furthermore, our lab and other groups have recently shown that αSYN can adopt distinct fibril conformations or ?strains? with varying levels of pathogenic impact. Therefore, the aim of this study was to assess the impact of peripheral inflammation on αSYN spreading in order to better understand the participation of the immune system in the progression of PD. The results presented here show that intraperitoneal LPS injection prior to systemic intravenous recombinant administration of two different αSYN pathogenic strains (fibrils or ribbons) in wild type mice, induces an increase in brain resident microglia and promotes the recruitment of leukocytes toward the brain and the spinal cord. Our findings show for the first time that αSYN can be internalized by LPS-primed inflammatory monocytes, which in turn favors the dissemination from the periphery toward the brain and spinal cord. Further, we found a differential recruitment of CD4+ and CD8+ T cells after LPS priming and subsequent administration of the αSYN ribbons strain. Together, these data argue for a role of the peripheral immune system in αSYN pathology.
Fil: Peralta Ramos, Javier María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Iribarren, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Bousset, Luc. Institut François Jacob; Francia
Fil: Melki, Ronald. Institut François Jacob; Francia
Fil: Baekelandt, Veerle. Katholikie Universiteit Leuven; Bélgica
Fil: Van der Perren, Anke. Katholikie Universiteit Leuven; Bélgica
Materia
ALPHA-SYNUCLEIN
INFLAMMATION
INFLAMMATORY MONOCYTES
PARKINSON'S DISEASE
SYNUCLEINOPATHIES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/128718
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/128718
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administrationPeralta Ramos, Javier MaríaIribarren, PabloBousset, LucMelki, RonaldBaekelandt, VeerleVan der Perren, AnkeALPHA-SYNUCLEININFLAMMATIONINFLAMMATORY MONOCYTESPARKINSON'S DISEASESYNUCLEINOPATHIEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Innate immune activation and chronic neuroinflammation are characteristic features of many neurodegenerative diseases including Parkinson´s disease (PD) and may contribute to the pathophysiology of the disease. The discovery of misfolded alpha-synuclein (αSYN) protein aggregates, which amplify in a ?prion-like? fashion, has led us to consider that pathogenic αSYN might be hijacking the activation and mobilization mechanism of the peripheral immune system to reach and disseminate within the CNS. Furthermore, our lab and other groups have recently shown that αSYN can adopt distinct fibril conformations or ?strains? with varying levels of pathogenic impact. Therefore, the aim of this study was to assess the impact of peripheral inflammation on αSYN spreading in order to better understand the participation of the immune system in the progression of PD. The results presented here show that intraperitoneal LPS injection prior to systemic intravenous recombinant administration of two different αSYN pathogenic strains (fibrils or ribbons) in wild type mice, induces an increase in brain resident microglia and promotes the recruitment of leukocytes toward the brain and the spinal cord. Our findings show for the first time that αSYN can be internalized by LPS-primed inflammatory monocytes, which in turn favors the dissemination from the periphery toward the brain and spinal cord. Further, we found a differential recruitment of CD4+ and CD8+ T cells after LPS priming and subsequent administration of the αSYN ribbons strain. Together, these data argue for a role of the peripheral immune system in αSYN pathology.Fil: Peralta Ramos, Javier María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Iribarren, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bousset, Luc. Institut François Jacob; FranciaFil: Melki, Ronald. Institut François Jacob; FranciaFil: Baekelandt, Veerle. Katholikie Universiteit Leuven; BélgicaFil: Van der Perren, Anke. Katholikie Universiteit Leuven; BélgicaFrontiers Media S.A.2019-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/128718Peralta Ramos, Javier María; Iribarren, Pablo; Bousset, Luc; Melki, Ronald; Baekelandt, Veerle; et al.; Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration; Frontiers Media S.A.; Frontiers in Immunology; 10; JAN; 1-2019; 1-61664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.00080info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2019.00080/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:29:09Zoai:ri.conicet.gov.ar:11336/128718instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:29:09.866CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration
title Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration
spellingShingle Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration
Peralta Ramos, Javier María
ALPHA-SYNUCLEIN
INFLAMMATION
INFLAMMATORY MONOCYTES
PARKINSON'S DISEASE
SYNUCLEINOPATHIES
title_short Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration
title_full Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration
title_fullStr Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration
title_full_unstemmed Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration
title_sort Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration
dc.creator.none.fl_str_mv Peralta Ramos, Javier María
Iribarren, Pablo
Bousset, Luc
Melki, Ronald
Baekelandt, Veerle
Van der Perren, Anke
author Peralta Ramos, Javier María
author_facet Peralta Ramos, Javier María
Iribarren, Pablo
Bousset, Luc
Melki, Ronald
Baekelandt, Veerle
Van der Perren, Anke
author_role author
author2 Iribarren, Pablo
Bousset, Luc
Melki, Ronald
Baekelandt, Veerle
Van der Perren, Anke
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ALPHA-SYNUCLEIN
INFLAMMATION
INFLAMMATORY MONOCYTES
PARKINSON'S DISEASE
SYNUCLEINOPATHIES
topic ALPHA-SYNUCLEIN
INFLAMMATION
INFLAMMATORY MONOCYTES
PARKINSON'S DISEASE
SYNUCLEINOPATHIES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Innate immune activation and chronic neuroinflammation are characteristic features of many neurodegenerative diseases including Parkinson´s disease (PD) and may contribute to the pathophysiology of the disease. The discovery of misfolded alpha-synuclein (αSYN) protein aggregates, which amplify in a ?prion-like? fashion, has led us to consider that pathogenic αSYN might be hijacking the activation and mobilization mechanism of the peripheral immune system to reach and disseminate within the CNS. Furthermore, our lab and other groups have recently shown that αSYN can adopt distinct fibril conformations or ?strains? with varying levels of pathogenic impact. Therefore, the aim of this study was to assess the impact of peripheral inflammation on αSYN spreading in order to better understand the participation of the immune system in the progression of PD. The results presented here show that intraperitoneal LPS injection prior to systemic intravenous recombinant administration of two different αSYN pathogenic strains (fibrils or ribbons) in wild type mice, induces an increase in brain resident microglia and promotes the recruitment of leukocytes toward the brain and the spinal cord. Our findings show for the first time that αSYN can be internalized by LPS-primed inflammatory monocytes, which in turn favors the dissemination from the periphery toward the brain and spinal cord. Further, we found a differential recruitment of CD4+ and CD8+ T cells after LPS priming and subsequent administration of the αSYN ribbons strain. Together, these data argue for a role of the peripheral immune system in αSYN pathology.
Fil: Peralta Ramos, Javier María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Iribarren, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Bousset, Luc. Institut François Jacob; Francia
Fil: Melki, Ronald. Institut François Jacob; Francia
Fil: Baekelandt, Veerle. Katholikie Universiteit Leuven; Bélgica
Fil: Van der Perren, Anke. Katholikie Universiteit Leuven; Bélgica
description Innate immune activation and chronic neuroinflammation are characteristic features of many neurodegenerative diseases including Parkinson´s disease (PD) and may contribute to the pathophysiology of the disease. The discovery of misfolded alpha-synuclein (αSYN) protein aggregates, which amplify in a ?prion-like? fashion, has led us to consider that pathogenic αSYN might be hijacking the activation and mobilization mechanism of the peripheral immune system to reach and disseminate within the CNS. Furthermore, our lab and other groups have recently shown that αSYN can adopt distinct fibril conformations or ?strains? with varying levels of pathogenic impact. Therefore, the aim of this study was to assess the impact of peripheral inflammation on αSYN spreading in order to better understand the participation of the immune system in the progression of PD. The results presented here show that intraperitoneal LPS injection prior to systemic intravenous recombinant administration of two different αSYN pathogenic strains (fibrils or ribbons) in wild type mice, induces an increase in brain resident microglia and promotes the recruitment of leukocytes toward the brain and the spinal cord. Our findings show for the first time that αSYN can be internalized by LPS-primed inflammatory monocytes, which in turn favors the dissemination from the periphery toward the brain and spinal cord. Further, we found a differential recruitment of CD4+ and CD8+ T cells after LPS priming and subsequent administration of the αSYN ribbons strain. Together, these data argue for a role of the peripheral immune system in αSYN pathology.
publishDate 2019
dc.date.none.fl_str_mv 2019-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/128718
Peralta Ramos, Javier María; Iribarren, Pablo; Bousset, Luc; Melki, Ronald; Baekelandt, Veerle; et al.; Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration; Frontiers Media S.A.; Frontiers in Immunology; 10; JAN; 1-2019; 1-6
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/128718
identifier_str_mv Peralta Ramos, Javier María; Iribarren, Pablo; Bousset, Luc; Melki, Ronald; Baekelandt, Veerle; et al.; Peripheral inflammation regulates CNS immune surveillance through the recruitment of inflammatory monocytes upon systemic α-synuclein administration; Frontiers Media S.A.; Frontiers in Immunology; 10; JAN; 1-2019; 1-6
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.00080
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2019.00080/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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