The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria
Abstract Background Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controll...
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ftdoajarticles:oai:doaj.org/article:0193d8e284dd47609fc0be6ba801edee 2023-05-15T15:12:02+02:00 The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria Ana Villegas-Mendez Nicholas Stafford Michael J. Haley Normalita Eka Pravitasari Florence Baudoin Adnan Ali Puji Budi Setia Asih Josephine E. Siregar Esther Baena Din Syafruddin Kevin N. Couper Delvac Oceandy 2021-07-01T00:00:00Z https://doi.org/10.1186/s12936-021-03832-w https://doaj.org/article/0193d8e284dd47609fc0be6ba801edee EN eng BMC https://doi.org/10.1186/s12936-021-03832-w https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03832-w 1475-2875 https://doaj.org/article/0193d8e284dd47609fc0be6ba801edee Malaria Journal, Vol 20, Iss 1, Pp 1-16 (2021) PMCA4 Malaria Knockout mice Plasmodium Cerebral malaria Red blood cell Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2021 ftdoajarticles https://doi.org/10.1186/s12936-021-03832-w 2022-12-31T12:28:12Z Abstract Background Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controlling the physiological level of intracellular calcium in many cell types, including red blood cells (RBCs). It is, therefore, postulated that genetic differences in the activity or expression level of PMCA4 alters intracellular Ca2+ levels and affects RBC hydration, modulating the invasion and growth of the Plasmodium parasite within its target host cell. Methods In this study the course of three different Plasmodium spp. infections were examined in mice with systemic knockout of Pmca4 expression. Results Ablation of PMCA4 reduced the size of RBCs and their haemoglobin content but did not affect RBC maturation and reticulocyte count. Surprisingly, knockout of PMCA4 did not significantly alter peripheral parasite burdens or the dynamics of blood stage Plasmodium chabaudi infection or reticulocyte-restricted Plasmodium yoelii infection. Interestingly, although ablation of PMCA4 did not affect peripheral parasite levels during Plasmodium berghei infection, it did promote slight protection against experimental cerebral malaria, associated with a minor reduction in antigen-experienced T cell accumulation in the brain. Conclusions The finding suggests that PMCA4 may play a minor role in the development of severe malarial complications, but that this appears independent of direct effects on parasite invasion, growth or survival within RBCs. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 20 1 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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PMCA4 Malaria Knockout mice Plasmodium Cerebral malaria Red blood cell Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
PMCA4 Malaria Knockout mice Plasmodium Cerebral malaria Red blood cell Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Ana Villegas-Mendez Nicholas Stafford Michael J. Haley Normalita Eka Pravitasari Florence Baudoin Adnan Ali Puji Budi Setia Asih Josephine E. Siregar Esther Baena Din Syafruddin Kevin N. Couper Delvac Oceandy The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria |
topic_facet |
PMCA4 Malaria Knockout mice Plasmodium Cerebral malaria Red blood cell Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controlling the physiological level of intracellular calcium in many cell types, including red blood cells (RBCs). It is, therefore, postulated that genetic differences in the activity or expression level of PMCA4 alters intracellular Ca2+ levels and affects RBC hydration, modulating the invasion and growth of the Plasmodium parasite within its target host cell. Methods In this study the course of three different Plasmodium spp. infections were examined in mice with systemic knockout of Pmca4 expression. Results Ablation of PMCA4 reduced the size of RBCs and their haemoglobin content but did not affect RBC maturation and reticulocyte count. Surprisingly, knockout of PMCA4 did not significantly alter peripheral parasite burdens or the dynamics of blood stage Plasmodium chabaudi infection or reticulocyte-restricted Plasmodium yoelii infection. Interestingly, although ablation of PMCA4 did not affect peripheral parasite levels during Plasmodium berghei infection, it did promote slight protection against experimental cerebral malaria, associated with a minor reduction in antigen-experienced T cell accumulation in the brain. Conclusions The finding suggests that PMCA4 may play a minor role in the development of severe malarial complications, but that this appears independent of direct effects on parasite invasion, growth or survival within RBCs. |
format |
Article in Journal/Newspaper |
author |
Ana Villegas-Mendez Nicholas Stafford Michael J. Haley Normalita Eka Pravitasari Florence Baudoin Adnan Ali Puji Budi Setia Asih Josephine E. Siregar Esther Baena Din Syafruddin Kevin N. Couper Delvac Oceandy |
author_facet |
Ana Villegas-Mendez Nicholas Stafford Michael J. Haley Normalita Eka Pravitasari Florence Baudoin Adnan Ali Puji Budi Setia Asih Josephine E. Siregar Esther Baena Din Syafruddin Kevin N. Couper Delvac Oceandy |
author_sort |
Ana Villegas-Mendez |
title |
The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria |
title_short |
The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria |
title_full |
The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria |
title_fullStr |
The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria |
title_full_unstemmed |
The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria |
title_sort |
plasma membrane calcium atpase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria |
publisher |
BMC |
publishDate |
2021 |
url |
https://doi.org/10.1186/s12936-021-03832-w https://doaj.org/article/0193d8e284dd47609fc0be6ba801edee |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 20, Iss 1, Pp 1-16 (2021) |
op_relation |
https://doi.org/10.1186/s12936-021-03832-w https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03832-w 1475-2875 https://doaj.org/article/0193d8e284dd47609fc0be6ba801edee |
op_doi |
https://doi.org/10.1186/s12936-021-03832-w |
container_title |
Malaria Journal |
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20 |
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1 |
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1766342782504402944 |