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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
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.
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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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