Cargando…

Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus

Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler’s murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on com...

Descripción completa

Detalles Bibliográficos
Autores principales: Carrillo-Salinas, F. J., Mestre, L., Mecha, M., Feliú, A., del Campo, R., Villarrubia, N., Espejo, C., Montalbán, X., Álvarez-Cermeño, J. C., Villar, L. M., Guaza, C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349526/
https://www.ncbi.nlm.nih.gov/pubmed/28290524
http://dx.doi.org/10.1038/srep44377
_version_ 1782514484274790400
author Carrillo-Salinas, F. J.
Mestre, L.
Mecha, M.
Feliú, A.
del Campo, R.
Villarrubia, N.
Espejo, C.
Montalbán, X.
Álvarez-Cermeño, J. C.
Villar, L. M.
Guaza, C.
author_facet Carrillo-Salinas, F. J.
Mestre, L.
Mecha, M.
Feliú, A.
del Campo, R.
Villarrubia, N.
Espejo, C.
Montalbán, X.
Álvarez-Cermeño, J. C.
Villar, L. M.
Guaza, C.
author_sort Carrillo-Salinas, F. J.
collection PubMed
description Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler’s murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4(+) and CD8(+) T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4(+) and CD8(+)T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice.
format Online
Article
Text
id pubmed-5349526
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-53495262017-03-17 Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus Carrillo-Salinas, F. J. Mestre, L. Mecha, M. Feliú, A. del Campo, R. Villarrubia, N. Espejo, C. Montalbán, X. Álvarez-Cermeño, J. C. Villar, L. M. Guaza, C. Sci Rep Article Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler’s murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4(+) and CD8(+) T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4(+) and CD8(+)T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice. Nature Publishing Group 2017-03-14 /pmc/articles/PMC5349526/ /pubmed/28290524 http://dx.doi.org/10.1038/srep44377 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Carrillo-Salinas, F. J.
Mestre, L.
Mecha, M.
Feliú, A.
del Campo, R.
Villarrubia, N.
Espejo, C.
Montalbán, X.
Álvarez-Cermeño, J. C.
Villar, L. M.
Guaza, C.
Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus
title Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus
title_full Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus
title_fullStr Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus
title_full_unstemmed Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus
title_short Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus
title_sort gut dysbiosis and neuroimmune responses to brain infection with theiler’s murine encephalomyelitis virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349526/
https://www.ncbi.nlm.nih.gov/pubmed/28290524
http://dx.doi.org/10.1038/srep44377
work_keys_str_mv AT carrillosalinasfj gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT mestrel gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT mecham gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT feliua gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT delcampor gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT villarrubian gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT espejoc gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT montalbanx gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT alvarezcermenojc gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT villarlm gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus
AT guazac gutdysbiosisandneuroimmuneresponsestobraininfectionwiththeilersmurineencephalomyelitisvirus