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Peripheral Inflammation Regulates CNS Immune Surveillance Through the Recruitment of Inflammatory Monocytes Upon Systemic α-Synuclein Administration
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361759/ https://www.ncbi.nlm.nih.gov/pubmed/30761145 http://dx.doi.org/10.3389/fimmu.2019.00080 |
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author | Peralta Ramos, Javier María Iribarren, Pablo Bousset, Luc Melki, Ronald Baekelandt, Veerle Van der Perren, Anke |
author_facet | Peralta Ramos, Javier María Iribarren, Pablo Bousset, Luc Melki, Ronald Baekelandt, Veerle Van der Perren, Anke |
author_sort | Peralta Ramos, Javier María |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6361759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63617592019-02-13 Peripheral Inflammation Regulates CNS Immune Surveillance Through the Recruitment of Inflammatory Monocytes Upon Systemic α-Synuclein Administration Peralta Ramos, Javier María Iribarren, Pablo Bousset, Luc Melki, Ronald Baekelandt, Veerle Van der Perren, Anke Front Immunol Immunology 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. Frontiers Media S.A. 2019-01-29 /pmc/articles/PMC6361759/ /pubmed/30761145 http://dx.doi.org/10.3389/fimmu.2019.00080 Text en Copyright © 2019 Peralta Ramos, Iribarren, Bousset, Melki, Baekelandt and Van der Perren. http://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 | Immunology Peralta Ramos, Javier María Iribarren, Pablo Bousset, Luc Melki, Ronald Baekelandt, Veerle Van der Perren, Anke 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 |
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_short | 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 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361759/ https://www.ncbi.nlm.nih.gov/pubmed/30761145 http://dx.doi.org/10.3389/fimmu.2019.00080 |
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