An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes

Abstract Malaria has been one of the strongest selective forces on the human genome. The increased frequency of haemoglobinopathies, as well as numerous other blood groups, in malaria endemic regions is commonly attributed to a protective effect of these alleles against malaria. In the majority of t...

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Main Authors: Michel Theron, Nadia Cross, Paula Cawkill, Leyla Y. Bustamante, Julian C. Rayner
Format: Article
Language:English
Published: Nature Publishing Group 2018-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-018-26559-2
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spelling doaj-3a806973083046ed9497d5247a752ae02020-12-08T05:15:50ZengNature Publishing GroupScientific Reports2045-23222018-05-01811910.1038/s41598-018-26559-2An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytesMichel Theron0Nadia Cross1Paula Cawkill2Leyla Y. Bustamante3Julian C. Rayner4Malaria Programme, Wellcome Sanger Institute, Wellcome Genome Campus, HinxtonMalaria Programme, Wellcome Sanger Institute, Wellcome Genome Campus, HinxtonMalaria Programme, Wellcome Sanger Institute, Wellcome Genome Campus, HinxtonMalaria Programme, Wellcome Sanger Institute, Wellcome Genome Campus, HinxtonMalaria Programme, Wellcome Sanger Institute, Wellcome Genome Campus, HinxtonAbstract Malaria has been one of the strongest selective forces on the human genome. The increased frequency of haemoglobinopathies, as well as numerous other blood groups, in malaria endemic regions is commonly attributed to a protective effect of these alleles against malaria. In the majority of these cases however there have been no systematic functional studies to test protective mechanisms, in large part because most host-parasite interaction assays are not quantitative or scalable. We describe the development of an erythrocyte preference assay which uses differential labelling with fluorescent dyes to distinguish invasion into four different erythrocyte populations which are all co-incubated with a single Plasmodium falciparum parasite culture. Testing this assay on erythrocytes across the ABO blood system from forty independent donors reveals for the first time that P. falciparum parasites preferentially invade group O over Group A erythrocytes. This runs counter to the known protective effect of group O against severe malaria, but emphasises the complexities of host-pathogen interactions, and the need for highly quantitative and scalable assays to systematically explore them.https://doi.org/10.1038/s41598-018-26559-2
collection DOAJ
language English
format Article
sources DOAJ
author Michel Theron
Nadia Cross
Paula Cawkill
Leyla Y. Bustamante
Julian C. Rayner
spellingShingle Michel Theron
Nadia Cross
Paula Cawkill
Leyla Y. Bustamante
Julian C. Rayner
An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes
Scientific Reports
author_facet Michel Theron
Nadia Cross
Paula Cawkill
Leyla Y. Bustamante
Julian C. Rayner
author_sort Michel Theron
title An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes
title_short An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes
title_full An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes
title_fullStr An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes
title_full_unstemmed An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes
title_sort in vitro erythrocyte preference assay reveals that plasmodium falciparum parasites prefer type o over type a erythrocytes
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2018-05-01
description Abstract Malaria has been one of the strongest selective forces on the human genome. The increased frequency of haemoglobinopathies, as well as numerous other blood groups, in malaria endemic regions is commonly attributed to a protective effect of these alleles against malaria. In the majority of these cases however there have been no systematic functional studies to test protective mechanisms, in large part because most host-parasite interaction assays are not quantitative or scalable. We describe the development of an erythrocyte preference assay which uses differential labelling with fluorescent dyes to distinguish invasion into four different erythrocyte populations which are all co-incubated with a single Plasmodium falciparum parasite culture. Testing this assay on erythrocytes across the ABO blood system from forty independent donors reveals for the first time that P. falciparum parasites preferentially invade group O over Group A erythrocytes. This runs counter to the known protective effect of group O against severe malaria, but emphasises the complexities of host-pathogen interactions, and the need for highly quantitative and scalable assays to systematically explore them.
url https://doi.org/10.1038/s41598-018-26559-2
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