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Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation
Trypanosoma brucei is a protozoan parasite that evades its host’s adaptive immune response by repeatedly replacing its dense variant surface glycoprotein (VSG) coat from its large genomic VSG repertoire. While the mechanisms regulating VSG gene expression and diversification have been examined exten...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635023/ https://www.ncbi.nlm.nih.gov/pubmed/29018220 http://dx.doi.org/10.1038/s41467-017-00959-w |
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author | Pinger, Jason Chowdhury, Shanin Papavasiliou, F. Nina |
author_facet | Pinger, Jason Chowdhury, Shanin Papavasiliou, F. Nina |
author_sort | Pinger, Jason |
collection | PubMed |
description | Trypanosoma brucei is a protozoan parasite that evades its host’s adaptive immune response by repeatedly replacing its dense variant surface glycoprotein (VSG) coat from its large genomic VSG repertoire. While the mechanisms regulating VSG gene expression and diversification have been examined extensively, the dynamics of VSG coat replacement at the protein level, and the impact of this process on successful immune evasion, remain unclear. Here we evaluate the rate of VSG replacement at the trypanosome surface following a genetic VSG switch, and show that full coat replacement requires several days to complete. Using in vivo infection assays, we demonstrate that parasites undergoing coat replacement are only vulnerable to clearance via early IgM antibodies for a limited time. Finally, we show that IgM loses its ability to mediate trypanosome clearance at unexpectedly early stages of coat replacement based on a critical density threshold of its cognate VSGs on the parasite surface. |
format | Online Article Text |
id | pubmed-5635023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56350232017-10-12 Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation Pinger, Jason Chowdhury, Shanin Papavasiliou, F. Nina Nat Commun Article Trypanosoma brucei is a protozoan parasite that evades its host’s adaptive immune response by repeatedly replacing its dense variant surface glycoprotein (VSG) coat from its large genomic VSG repertoire. While the mechanisms regulating VSG gene expression and diversification have been examined extensively, the dynamics of VSG coat replacement at the protein level, and the impact of this process on successful immune evasion, remain unclear. Here we evaluate the rate of VSG replacement at the trypanosome surface following a genetic VSG switch, and show that full coat replacement requires several days to complete. Using in vivo infection assays, we demonstrate that parasites undergoing coat replacement are only vulnerable to clearance via early IgM antibodies for a limited time. Finally, we show that IgM loses its ability to mediate trypanosome clearance at unexpectedly early stages of coat replacement based on a critical density threshold of its cognate VSGs on the parasite surface. Nature Publishing Group UK 2017-10-10 /pmc/articles/PMC5635023/ /pubmed/29018220 http://dx.doi.org/10.1038/s41467-017-00959-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Pinger, Jason Chowdhury, Shanin Papavasiliou, F. Nina Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation |
title | Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation |
title_full | Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation |
title_fullStr | Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation |
title_full_unstemmed | Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation |
title_short | Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation |
title_sort | variant surface glycoprotein density defines an immune evasion threshold for african trypanosomes undergoing antigenic variation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635023/ https://www.ncbi.nlm.nih.gov/pubmed/29018220 http://dx.doi.org/10.1038/s41467-017-00959-w |
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