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Toll-like Receptor 7 Controls the Anti-Retroviral Germinal Center Response

The development of vaccines that can enhance immunity to viral pathogens is an important goal. However, the innate molecular pathways that regulate the strength and quality of the immune response remain largely uncharacterized. To define the role of Toll-like receptor (TLR) signaling in control of a...

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Autor principal: Browne, Edward P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188541/
https://www.ncbi.nlm.nih.gov/pubmed/21998589
http://dx.doi.org/10.1371/journal.ppat.1002293
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author Browne, Edward P.
author_facet Browne, Edward P.
author_sort Browne, Edward P.
collection PubMed
description The development of vaccines that can enhance immunity to viral pathogens is an important goal. However, the innate molecular pathways that regulate the strength and quality of the immune response remain largely uncharacterized. To define the role of Toll-like receptor (TLR) signaling in control of a model retroviral pathogen, Friend virus (FV), I generated mice in which the TLR signaling adapter Myd88 was selectively deleted in dendritic cell (DC) or in B cell lineages. Deletion of Myd88 in DCs had little effect on immune control of FV, while B cell specific deletion of Myd88 caused a dramatic increase in viral infectious centers and a significantly reduced antibody response, indicating that B cell-intrinsic TLR signaling plays a crucial role, while TLR signaling in DCs is less important. I then identified the single-stranded RNA sensing protein TLR7 as being required for antibody-mediated control of FV by analyzing mice deficient in TLR7. Remarkably, B cells in infected TLR7-deficient mice upregulated CD69 and CD86 early in infection, but failed to develop into germinal center B cells. CD4 T cell responses were also attenuated in the absence of TLR7, but CD8 responses were TLR7 independent, suggesting the existence of additional pathways for detection of retroviral particles. Together these results demonstrate that the vertebrate immune system detects retroviruses in vivo via TLR7 and that this pathway regulates a key checkpoint controlling development of germinal center B cells.
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spelling pubmed-31885412011-10-13 Toll-like Receptor 7 Controls the Anti-Retroviral Germinal Center Response Browne, Edward P. PLoS Pathog Research Article The development of vaccines that can enhance immunity to viral pathogens is an important goal. However, the innate molecular pathways that regulate the strength and quality of the immune response remain largely uncharacterized. To define the role of Toll-like receptor (TLR) signaling in control of a model retroviral pathogen, Friend virus (FV), I generated mice in which the TLR signaling adapter Myd88 was selectively deleted in dendritic cell (DC) or in B cell lineages. Deletion of Myd88 in DCs had little effect on immune control of FV, while B cell specific deletion of Myd88 caused a dramatic increase in viral infectious centers and a significantly reduced antibody response, indicating that B cell-intrinsic TLR signaling plays a crucial role, while TLR signaling in DCs is less important. I then identified the single-stranded RNA sensing protein TLR7 as being required for antibody-mediated control of FV by analyzing mice deficient in TLR7. Remarkably, B cells in infected TLR7-deficient mice upregulated CD69 and CD86 early in infection, but failed to develop into germinal center B cells. CD4 T cell responses were also attenuated in the absence of TLR7, but CD8 responses were TLR7 independent, suggesting the existence of additional pathways for detection of retroviral particles. Together these results demonstrate that the vertebrate immune system detects retroviruses in vivo via TLR7 and that this pathway regulates a key checkpoint controlling development of germinal center B cells. Public Library of Science 2011-10-06 /pmc/articles/PMC3188541/ /pubmed/21998589 http://dx.doi.org/10.1371/journal.ppat.1002293 Text en Edward P. Browne. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Browne, Edward P.
Toll-like Receptor 7 Controls the Anti-Retroviral Germinal Center Response
title Toll-like Receptor 7 Controls the Anti-Retroviral Germinal Center Response
title_full Toll-like Receptor 7 Controls the Anti-Retroviral Germinal Center Response
title_fullStr Toll-like Receptor 7 Controls the Anti-Retroviral Germinal Center Response
title_full_unstemmed Toll-like Receptor 7 Controls the Anti-Retroviral Germinal Center Response
title_short Toll-like Receptor 7 Controls the Anti-Retroviral Germinal Center Response
title_sort toll-like receptor 7 controls the anti-retroviral germinal center response
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188541/
https://www.ncbi.nlm.nih.gov/pubmed/21998589
http://dx.doi.org/10.1371/journal.ppat.1002293
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