Mycolactone displays anti-inflammatory effects on the nervous system.
Mycolactone is a macrolide produced by the skin pathogen Mycobacterium ulcerans, with cytotoxic, analgesic and immunomodulatory properties. The latter were recently shown to result from mycolactone blocking the Sec61-dependent production of pro-inflammatory mediators by immune cells. Here we investi...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2017
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0006058 https://doaj.org/article/aa52f474023e4c9bbd6c4c41e5e01010 |
id |
ftdoajarticles:oai:doaj.org/article:aa52f474023e4c9bbd6c4c41e5e01010 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:aa52f474023e4c9bbd6c4c41e5e01010 2023-05-15T15:12:15+02:00 Mycolactone displays anti-inflammatory effects on the nervous system. Caroline Isaac Annie Mauborgne Alfonso Grimaldi Kemy Ade Michel Pohl Cristina Limatola Yves Boucher Caroline Demangel Laure Guenin-Macé 2017-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006058 https://doaj.org/article/aa52f474023e4c9bbd6c4c41e5e01010 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5693295?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006058 https://doaj.org/article/aa52f474023e4c9bbd6c4c41e5e01010 PLoS Neglected Tropical Diseases, Vol 11, Iss 11, p e0006058 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006058 2022-12-31T06:28:13Z Mycolactone is a macrolide produced by the skin pathogen Mycobacterium ulcerans, with cytotoxic, analgesic and immunomodulatory properties. The latter were recently shown to result from mycolactone blocking the Sec61-dependent production of pro-inflammatory mediators by immune cells. Here we investigated whether mycolactone similarly affects the inflammatory responses of the nervous cell subsets involved in pain perception, transmission and maintenance. We also investigated the effects of mycolactone on the neuroinflammation that is associated with chronic pain in vivo.Sensory neurons, Schwann cells and microglia were isolated from mice for ex vivo assessment of mycolactone cytotoxicity and immunomodulatory activity by measuring the production of proalgesic cytokines and chemokines. In all cell types studied, prolonged (>48h) exposure to mycolactone induced significant cell death at concentrations >10 ng/ml. Within the first 24h treatment, nanomolar concentrations of mycolactone efficiently suppressed the cell production of pro-inflammatory mediators, without affecting their viability. Notably, mycolactone also prevented the pro-inflammatory polarization of cortical microglia. Since these cells critically contribute to neuroinflammation, we next tested if mycolactone impacts this pathogenic process in vivo. We used a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. Here, mycolactone was injected daily for 3 days in the spinal canal, to ensure its proper delivery to spinal cord. While this treatment failed to prevent injury-induced neuroinflammation, it decreased significantly the local production of inflammatory cytokines without inducing detectable cytotoxicity.The present study provides in vitro and in vivo evidence that mycolactone suppresses the inflammatory responses of sensory neurons, Schwann cells and microglia, without affecting the cell viability. Together with previous studies using peripheral blood leukocytes, our work implies that mycolactone-mediated ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 11 e0006058 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Caroline Isaac Annie Mauborgne Alfonso Grimaldi Kemy Ade Michel Pohl Cristina Limatola Yves Boucher Caroline Demangel Laure Guenin-Macé Mycolactone displays anti-inflammatory effects on the nervous system. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Mycolactone is a macrolide produced by the skin pathogen Mycobacterium ulcerans, with cytotoxic, analgesic and immunomodulatory properties. The latter were recently shown to result from mycolactone blocking the Sec61-dependent production of pro-inflammatory mediators by immune cells. Here we investigated whether mycolactone similarly affects the inflammatory responses of the nervous cell subsets involved in pain perception, transmission and maintenance. We also investigated the effects of mycolactone on the neuroinflammation that is associated with chronic pain in vivo.Sensory neurons, Schwann cells and microglia were isolated from mice for ex vivo assessment of mycolactone cytotoxicity and immunomodulatory activity by measuring the production of proalgesic cytokines and chemokines. In all cell types studied, prolonged (>48h) exposure to mycolactone induced significant cell death at concentrations >10 ng/ml. Within the first 24h treatment, nanomolar concentrations of mycolactone efficiently suppressed the cell production of pro-inflammatory mediators, without affecting their viability. Notably, mycolactone also prevented the pro-inflammatory polarization of cortical microglia. Since these cells critically contribute to neuroinflammation, we next tested if mycolactone impacts this pathogenic process in vivo. We used a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. Here, mycolactone was injected daily for 3 days in the spinal canal, to ensure its proper delivery to spinal cord. While this treatment failed to prevent injury-induced neuroinflammation, it decreased significantly the local production of inflammatory cytokines without inducing detectable cytotoxicity.The present study provides in vitro and in vivo evidence that mycolactone suppresses the inflammatory responses of sensory neurons, Schwann cells and microglia, without affecting the cell viability. Together with previous studies using peripheral blood leukocytes, our work implies that mycolactone-mediated ... |
format |
Article in Journal/Newspaper |
author |
Caroline Isaac Annie Mauborgne Alfonso Grimaldi Kemy Ade Michel Pohl Cristina Limatola Yves Boucher Caroline Demangel Laure Guenin-Macé |
author_facet |
Caroline Isaac Annie Mauborgne Alfonso Grimaldi Kemy Ade Michel Pohl Cristina Limatola Yves Boucher Caroline Demangel Laure Guenin-Macé |
author_sort |
Caroline Isaac |
title |
Mycolactone displays anti-inflammatory effects on the nervous system. |
title_short |
Mycolactone displays anti-inflammatory effects on the nervous system. |
title_full |
Mycolactone displays anti-inflammatory effects on the nervous system. |
title_fullStr |
Mycolactone displays anti-inflammatory effects on the nervous system. |
title_full_unstemmed |
Mycolactone displays anti-inflammatory effects on the nervous system. |
title_sort |
mycolactone displays anti-inflammatory effects on the nervous system. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0006058 https://doaj.org/article/aa52f474023e4c9bbd6c4c41e5e01010 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 11, p e0006058 (2017) |
op_relation |
http://europepmc.org/articles/PMC5693295?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006058 https://doaj.org/article/aa52f474023e4c9bbd6c4c41e5e01010 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006058 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
11 |
container_start_page |
e0006058 |
_version_ |
1766342958073774080 |