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Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo
Plasmodium falciparum has developed extensive mechanisms to evade host immune clearance. Currently, most of our understanding is based on in vitro studies of individual parasite variant surface antigens and how this relates to the processes in vivo is not well-understood. Here, we have used a humani...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279368/ https://www.ncbi.nlm.nih.gov/pubmed/35831417 http://dx.doi.org/10.1038/s41467-022-31741-2 |
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author | Chew, Marvin Ye, Weijian Omelianczyk, Radoslaw Igor Pasaje, Charisse Flerida Hoo, Regina Chen, Qingfeng Niles, Jacquin C. Chen, Jianzhu Preiser, Peter |
author_facet | Chew, Marvin Ye, Weijian Omelianczyk, Radoslaw Igor Pasaje, Charisse Flerida Hoo, Regina Chen, Qingfeng Niles, Jacquin C. Chen, Jianzhu Preiser, Peter |
author_sort | Chew, Marvin |
collection | PubMed |
description | Plasmodium falciparum has developed extensive mechanisms to evade host immune clearance. Currently, most of our understanding is based on in vitro studies of individual parasite variant surface antigens and how this relates to the processes in vivo is not well-understood. Here, we have used a humanized mouse model to identify parasite factors important for in vivo growth. We show that upregulation of the specific PfEMP1, VAR2CSA, provides the parasite with protection from macrophage phagocytosis and clearance in the humanized mice. Furthermore, parasites adapted to thrive in the humanized mice show reduced NK cell-mediated killing through interaction with the immune inhibitory receptor, LILRB1. Taken together, these findings reveal new insights into the molecular and cellular mechanisms that the parasite utilizes to coordinate immune escape in vivo. Identification and targeting of these specific parasite variant surface antigens crucial for immune evasion provides a unique approach for therapy. |
format | Online Article Text |
id | pubmed-9279368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92793682022-07-15 Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo Chew, Marvin Ye, Weijian Omelianczyk, Radoslaw Igor Pasaje, Charisse Flerida Hoo, Regina Chen, Qingfeng Niles, Jacquin C. Chen, Jianzhu Preiser, Peter Nat Commun Article Plasmodium falciparum has developed extensive mechanisms to evade host immune clearance. Currently, most of our understanding is based on in vitro studies of individual parasite variant surface antigens and how this relates to the processes in vivo is not well-understood. Here, we have used a humanized mouse model to identify parasite factors important for in vivo growth. We show that upregulation of the specific PfEMP1, VAR2CSA, provides the parasite with protection from macrophage phagocytosis and clearance in the humanized mice. Furthermore, parasites adapted to thrive in the humanized mice show reduced NK cell-mediated killing through interaction with the immune inhibitory receptor, LILRB1. Taken together, these findings reveal new insights into the molecular and cellular mechanisms that the parasite utilizes to coordinate immune escape in vivo. Identification and targeting of these specific parasite variant surface antigens crucial for immune evasion provides a unique approach for therapy. Nature Publishing Group UK 2022-07-13 /pmc/articles/PMC9279368/ /pubmed/35831417 http://dx.doi.org/10.1038/s41467-022-31741-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chew, Marvin Ye, Weijian Omelianczyk, Radoslaw Igor Pasaje, Charisse Flerida Hoo, Regina Chen, Qingfeng Niles, Jacquin C. Chen, Jianzhu Preiser, Peter Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo |
title | Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo |
title_full | Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo |
title_fullStr | Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo |
title_full_unstemmed | Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo |
title_short | Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo |
title_sort | selective expression of variant surface antigens enables plasmodium falciparum to evade immune clearance in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279368/ https://www.ncbi.nlm.nih.gov/pubmed/35831417 http://dx.doi.org/10.1038/s41467-022-31741-2 |
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