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Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure

BACKGROUND: The PfEMP1 family of Plasmodium falciparum antigens play a key role in pathogenesis of severe malaria through their insertion into the surface of parasite infected erythrocytes, and adhesion to host cells. Previous studies have suggested that parasites expressing PfEMP1 subclasses group...

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Autores principales: Abdi, Abdirahman I., Hodgson, Susanne H., Muthui, Michelle K., Kivisi, Cheryl A., Kamuyu, Gathoni, Kimani, Domtila, Hoffman, Stephen L., Juma, Elizabeth, Ogutu, Bernhards, Draper, Simon J., Osier, Faith, Bejon, Philip, Marsh, Kevin, Bull, Peter C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569527/
https://www.ncbi.nlm.nih.gov/pubmed/28835215
http://dx.doi.org/10.1186/s12879-017-2686-0
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author Abdi, Abdirahman I.
Hodgson, Susanne H.
Muthui, Michelle K.
Kivisi, Cheryl A.
Kamuyu, Gathoni
Kimani, Domtila
Hoffman, Stephen L.
Juma, Elizabeth
Ogutu, Bernhards
Draper, Simon J.
Osier, Faith
Bejon, Philip
Marsh, Kevin
Bull, Peter C.
author_facet Abdi, Abdirahman I.
Hodgson, Susanne H.
Muthui, Michelle K.
Kivisi, Cheryl A.
Kamuyu, Gathoni
Kimani, Domtila
Hoffman, Stephen L.
Juma, Elizabeth
Ogutu, Bernhards
Draper, Simon J.
Osier, Faith
Bejon, Philip
Marsh, Kevin
Bull, Peter C.
author_sort Abdi, Abdirahman I.
collection PubMed
description BACKGROUND: The PfEMP1 family of Plasmodium falciparum antigens play a key role in pathogenesis of severe malaria through their insertion into the surface of parasite infected erythrocytes, and adhesion to host cells. Previous studies have suggested that parasites expressing PfEMP1 subclasses group A and DC8, associated with severe malaria, may have a growth advantage in immunologically naïve individuals. However, this idea has not been tested in longitudinal studies. METHODS: Here we assessed expression of the var genes encoding PfEMP1, in parasites sampled from volunteers with varying prior exposure to malaria, following experimental infection by sporozoites (PfSPZ). Using qPCR, we tested for associations between the expression of various var subgroups in surviving parasite populations from each volunteer and 1) the levels of participants’ antibodies to infected erythrocytes before challenge infection and 2) the apparent in vivo parasite multiplication rate. RESULTS: We show that 1) expression of var genes encoding for group A and DC8-like PfEMP1 were associated with low levels of antibodies to infected erythrocytes (αIE) before challenge, and 2) expression of a DC8-like CIDRα1.1 domain was associated with higher apparent parasite multiplication rate in a manner that was independent of levels of prior antibodies to infected erythrocytes. CONCLUSIONS: This study provides insight into the role of antibodies to infected erythrocytes surface antigens in the development of naturally acquired immunity and may help explain why specific PfEMP1 variants may be associated with severe malaria. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR201211000433272. Date of registration: 10th October 2012.
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spelling pubmed-55695272017-08-29 Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure Abdi, Abdirahman I. Hodgson, Susanne H. Muthui, Michelle K. Kivisi, Cheryl A. Kamuyu, Gathoni Kimani, Domtila Hoffman, Stephen L. Juma, Elizabeth Ogutu, Bernhards Draper, Simon J. Osier, Faith Bejon, Philip Marsh, Kevin Bull, Peter C. BMC Infect Dis Research Article BACKGROUND: The PfEMP1 family of Plasmodium falciparum antigens play a key role in pathogenesis of severe malaria through their insertion into the surface of parasite infected erythrocytes, and adhesion to host cells. Previous studies have suggested that parasites expressing PfEMP1 subclasses group A and DC8, associated with severe malaria, may have a growth advantage in immunologically naïve individuals. However, this idea has not been tested in longitudinal studies. METHODS: Here we assessed expression of the var genes encoding PfEMP1, in parasites sampled from volunteers with varying prior exposure to malaria, following experimental infection by sporozoites (PfSPZ). Using qPCR, we tested for associations between the expression of various var subgroups in surviving parasite populations from each volunteer and 1) the levels of participants’ antibodies to infected erythrocytes before challenge infection and 2) the apparent in vivo parasite multiplication rate. RESULTS: We show that 1) expression of var genes encoding for group A and DC8-like PfEMP1 were associated with low levels of antibodies to infected erythrocytes (αIE) before challenge, and 2) expression of a DC8-like CIDRα1.1 domain was associated with higher apparent parasite multiplication rate in a manner that was independent of levels of prior antibodies to infected erythrocytes. CONCLUSIONS: This study provides insight into the role of antibodies to infected erythrocytes surface antigens in the development of naturally acquired immunity and may help explain why specific PfEMP1 variants may be associated with severe malaria. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR201211000433272. Date of registration: 10th October 2012. BioMed Central 2017-08-23 /pmc/articles/PMC5569527/ /pubmed/28835215 http://dx.doi.org/10.1186/s12879-017-2686-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Abdi, Abdirahman I.
Hodgson, Susanne H.
Muthui, Michelle K.
Kivisi, Cheryl A.
Kamuyu, Gathoni
Kimani, Domtila
Hoffman, Stephen L.
Juma, Elizabeth
Ogutu, Bernhards
Draper, Simon J.
Osier, Faith
Bejon, Philip
Marsh, Kevin
Bull, Peter C.
Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure
title Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure
title_full Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure
title_fullStr Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure
title_full_unstemmed Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure
title_short Plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of Kenyan adults with varying natural exposure
title_sort plasmodium falciparum malaria parasite var gene expression is modified by host antibodies: longitudinal evidence from controlled infections of kenyan adults with varying natural exposure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569527/
https://www.ncbi.nlm.nih.gov/pubmed/28835215
http://dx.doi.org/10.1186/s12879-017-2686-0
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