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The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling
Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through e...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634972/ https://www.ncbi.nlm.nih.gov/pubmed/31309928 http://dx.doi.org/10.7554/eLife.47117 |
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author | Brown, D Garrett Soto, Raymond Yandamuri, Soumya Stone, Colleen Dickey, Laura Gomes-Neto, Joao Carlos Pastuzyn, Elissa D Bell, Rickesha Petersen, Charisse Buhrke, Kaitlin Fujinami, Robert S O'Connell, Ryan M Stephens, W Zac Shepherd, Jason D Lane, Thomas E Round, June L |
author_facet | Brown, D Garrett Soto, Raymond Yandamuri, Soumya Stone, Colleen Dickey, Laura Gomes-Neto, Joao Carlos Pastuzyn, Elissa D Bell, Rickesha Petersen, Charisse Buhrke, Kaitlin Fujinami, Robert S O'Connell, Ryan M Stephens, W Zac Shepherd, Jason D Lane, Thomas E Round, June L |
author_sort | Brown, D Garrett |
collection | PubMed |
description | Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection. |
format | Online Article Text |
id | pubmed-6634972 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-66349722019-07-18 The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling Brown, D Garrett Soto, Raymond Yandamuri, Soumya Stone, Colleen Dickey, Laura Gomes-Neto, Joao Carlos Pastuzyn, Elissa D Bell, Rickesha Petersen, Charisse Buhrke, Kaitlin Fujinami, Robert S O'Connell, Ryan M Stephens, W Zac Shepherd, Jason D Lane, Thomas E Round, June L eLife Microbiology and Infectious Disease Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection. eLife Sciences Publications, Ltd 2019-07-16 /pmc/articles/PMC6634972/ /pubmed/31309928 http://dx.doi.org/10.7554/eLife.47117 Text en © 2019, Brown et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Microbiology and Infectious Disease Brown, D Garrett Soto, Raymond Yandamuri, Soumya Stone, Colleen Dickey, Laura Gomes-Neto, Joao Carlos Pastuzyn, Elissa D Bell, Rickesha Petersen, Charisse Buhrke, Kaitlin Fujinami, Robert S O'Connell, Ryan M Stephens, W Zac Shepherd, Jason D Lane, Thomas E Round, June L The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling |
title | The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling |
title_full | The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling |
title_fullStr | The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling |
title_full_unstemmed | The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling |
title_short | The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling |
title_sort | microbiota protects from viral-induced neurologic damage through microglia-intrinsic tlr signaling |
topic | Microbiology and Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634972/ https://www.ncbi.nlm.nih.gov/pubmed/31309928 http://dx.doi.org/10.7554/eLife.47117 |
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