The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria
Haley, M. J.
Pravitasari, N. E.
Asih, P. B. S.
Siregar, J. E.
Couper, K. N
AffiliationThe Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT,email@example.com.
MetadataShow full item record
AbstractBackground: 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.
CitationVillegas-Mendez A, Stafford N, Haley MJ, Pravitasari NE, Baudoin F, Ali A, et al. The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria. Malar J. 2021 Jul 2;20(1).
- Treatment with specific and pan-plasma membrane calcium ATPase (PMCA) inhibitors reduces malaria parasite growth in vitro and in vivo.
- Authors: Asih PBS, Siregar JE, Dewayanti FK, Pravitasari NE, Rozi IE, Rizki AFM, Risandi R, Couper KN, Oceandy D, Syafruddin D
- Issue date: 2022 Jun 29
- Cysteamine broadly improves the anti-plasmodial activity of artemisinins against murine blood stage and cerebral malaria.
- Authors: Moradin N, Torre S, Gauthier S, Tam M, Hawari J, Vandercruyssen K, De Spiegeleer B, Fortin A, Stevenson MM, Gros P
- Issue date: 2016 May 6
- Facilitation through altered resource availability in a mixed-species rodent malaria infection.
- Authors: Ramiro RS, Pollitt LC, Mideo N, Reece SE
- Issue date: 2016 Sep
- The Consequences of Mixed-Species Malaria Parasite Co-Infections in Mice and Mosquitoes for Disease Severity, Parasite Fitness, and Transmission Success.
- Authors: Tang J, Templeton TJ, Cao J, Culleton R
- Issue date: 2019
- An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility.
- Authors: Lessard S, Gatof ES, Beaudoin M, Schupp PG, Sher F, Ali A, Prehar S, Kurita R, Nakamura Y, Baena E, Ledoux J, Oceandy D, Bauer DE, Lettre G
- Issue date: 2017 Aug 1