scholarly journals A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Andrea Hernández-Castañeda ◽  
Marilyne Lavergne ◽  
Pierina Casanova ◽  
Bryan Nydegger ◽  
Carla Merten ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Molecular Mechanisms ◽  
Γδ T Cells ◽  
Parasite Growth ◽  
Complex Life Cycle ◽  
Cholesterol Depletion ◽  
Host Cell Membrane ◽  
Pore Forming Proteins

Malaria remains one of the most serious health problems in developing countries. The causative agent of malaria, Plasmodium spp., have a complex life cycle involving multiple developmental stages as well as different morphological, biochemical and metabolic requirements. We recently found that γδ T cells control parasite growth using pore-forming proteins to deliver their cytotoxic proteases, the granzymes, into blood residing parasites. Here, we follow up on the molecular mechanisms of parasite growth inhibition by human pore-forming proteins. We confirm that Plasmodium falciparum infection efficiently depletes the red blood cells of cholesterol, which renders the parasite surrounding membranes susceptible to lysis by prokaryotic membrane disrupting proteins, such as lymphocytic granulysin or the human cathelicidin LL-37. Interestingly, not the cholesterol depletion but rather the simultaneous exposure of phosphatidylserine, a negatively charged phospholipid, triggers resistance of late stage parasitized red blood cells towards the eukaryotic pore forming protein perforin. Overall, by revealing the molecular events we establish here a pathogen-host interaction that involves host cell membrane remodeling that defines the susceptibility towards cytolytic molecules.

scholarly journals Selective permeabilization of the host cell membrane of Plasmodium falciparum-infected red blood cells with streptolysin O and equinatoxin II

2007 ◽  
Vol 403 (1) ◽  
pp. 167-175 ◽  
Author(s):  
Katherine E. Jackson ◽  
Tobias Spielmann ◽  
Eric Hanssen ◽  
Akinola Adisa ◽  
Frances Separovic ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Membrane ◽  
Red Blood Cells ◽  
Host Cell ◽  
Blood Cells ◽  
Parasitophorous Vacuole ◽  
Host Cell Membrane ◽  
Streptolysin O ◽  
Infected Rbcs ◽  
Equinatoxin Ii

Plasmodium falciparum develops within the mature RBCs (red blood cells) of its human host in a PV (parasitophorous vacuole) that separates the host cell cytoplasm from the parasite surface. The pore-forming toxin, SLO (streptolysin O), binds to cholesterol-containing membranes and can be used to selectively permeabilize the host cell membrane while leaving the PV membrane intact. We found that in mixtures of infected and uninfected RBCs, SLO preferentially lyses uninfected RBCs rather than infected RBCs, presumably because of differences in cholesterol content of the limiting membrane. This provides a means of generating pure preparations of viable ring stage infected RBCs. As an alternative permeabilizing agent we have characterized EqtII (equinatoxin II), a eukaryotic pore-forming toxin that binds preferentially to sphingomyelin-containing membranes. EqtII lyses the limiting membrane of infected and uninfected RBCs with similar efficiency but does not disrupt the PV membrane. It generates pores of up to 100 nm, which allow entry of antibodies for immunofluorescence and immunogold labelling. The present study provides novel tools for the analysis of this important human pathogen and highlights differences between Plasmodium-infected and uninfected RBCs.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

Endothelin-1 production by a microvascular endothelial cell line treated with Plasmodium falciparum parasitized red blood cells

2002 ◽  
Vol 103 (s2002) ◽  
pp. 464S-466S ◽  
Author(s):  
Nicoletta BASILICO ◽  
Livianna SPECIALE ◽  
Silvia PARAPINI ◽  
Pasquale FERRANTE ◽  
Donatella TARAMELLI
Keyword(s):  
Plasmodium Falciparum ◽  
Endothelial Cell ◽  
Red Blood Cells ◽  
Cell Line ◽  
Blood Cells ◽  
Microvascular Endothelial Cell ◽  
Microvascular Endothelium ◽  
Endothelial Cell Line ◽  
Endothelin 1 ◽  
Microvascular Endothelial

In this study, we investigated the production of endothelin 1 (ET-1) by a human microvascular endothelial cell line, HMEC-1, co-cultured with Plasmodium falciparum-parasitized red blood cells (pRBCs). The results indicate that hypoxia increased the basal level of ET-1 production by HMEC-1 cells after 24 or 48h of treatment. However, the co-incubation of HMEC-1 cells with pRBCs, but not with uninfected RBCs, induced a dose-dependent decrease of both constitutive and hypoxia-induced ET-1 production. The inhibition was not due to a decrease in cell viability, as lactate dehydrogenase release remained constant. These results indicate that pRBCs are able to interfere with both the constitutive and stimulated ET-1 release from the microvascular endothelium, thus inducing local modifications of the vascular tone and of the inflammatory response. This could be of relevance in the pathogenesis of the most severe forms of P. falciparum infections, such as cerebral malaria or malaria during pregnancy.

scholarly journals Dielectric characterization of Plasmodium falciparum -infected red blood cells using microfluidic impedance cytometry

2018 ◽  
Vol 15 (147) ◽  
pp. 20180416 ◽  
Author(s):  
C. Honrado ◽  
L. Ciuffreda ◽  
D. Spencer ◽  
L. Ranford-Cartwright ◽  
H. Morgan
Keyword(s):  
Plasmodium Falciparum ◽  
Dielectric Properties ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Time Course ◽  
Fluorescent Protein ◽  
Clear Understanding ◽  
Infection Cycle ◽  
Dielectric Characterization ◽  
Impedance Cytometry

Although malaria is the world's most life-threatening parasitic disease, there is no clear understanding of how certain biophysical properties of infected cells change during the malaria infection cycle. In this article, we use microfluidic impedance cytometry to measure the dielectric properties of Plasmodium falciparum -infected red blood cells ( i- RBCs) at specific time points during the infection cycle. Individual parasites were identified within i- RBCs using green fluorescent protein (GFP) emission. The dielectric properties of cell sub-populations were determined using the multi-shell model. Analysis showed that the membrane capacitance and cytoplasmic conductivity of i- RBCs increased along the infection time course, due to membrane alterations caused by parasite infection. The volume ratio occupied by the parasite was estimated to vary from less than 10% at earlier stages, to approximately 90% at later stages. This knowledge could be used to develop new label-free cell sorting techniques for sample pre-enrichment, improving diagnosis.

scholarly journals Red blood cells release microparticles containing human argonaute 2 and miRNAs to target genes of Plasmodium falciparum

2017 ◽  
Vol 6 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Zhensheng Wang ◽  
Juemin Xi ◽  
Xiao Hao ◽  
Weiwei Deng ◽  
Juan Liu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Target Genes ◽  
Argonaute 2

scholarly journals Novel insights from the Plasmodium falciparum sporozoite-specific proteome by probabilistic integration of 26 studies

2021 ◽  
Vol 17 (4) ◽  
pp. e1008067
Author(s):  
Lisette Meerstein-Kessel ◽  
Jeron Venhuizen ◽  
Daniel Garza ◽  
Nicholas I. Proellochs ◽  
Emma J. Vos ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Salivary Glands ◽  
Molecular Mechanisms ◽  
Life Stage ◽  
Acid Synthesis ◽  
Complex Life Cycle ◽  
Quiescent State ◽  
Extended Phase ◽  
Human Host ◽  
Falciparum Sporozoite

Plasmodium species, the causative agent of malaria, have a complex life cycle involving two hosts. The sporozoite life stage is characterized by an extended phase in the mosquito salivary glands followed by free movement and rapid invasion of hepatocytes in the human host. This transmission stage has been the subject of many transcriptomics and proteomics studies and is also targeted by the most advanced malaria vaccine. We applied Bayesian data integration to determine which proteins are not only present in sporozoites but are also specific to that stage. Transcriptomic and proteomic Plasmodium data sets from 26 studies were weighted for how representative they are for sporozoites, based on a carefully assembled gold standard for Plasmodium falciparum (Pf) proteins known to be present or absent during the sporozoite life stage. Of 5418 Pf genes for which expression data were available at the RNA level or at the protein level, 975 were identified as enriched in sporozoites and 90 specific to them. We show that Pf sporozoites are enriched for proteins involved in type II fatty acid synthesis in the apicoplast and GPI anchor synthesis, but otherwise appear metabolically relatively inactive in the salivary glands of mosquitos. Newly annotated hypothetical sporozoite-specific and sporozoite-enriched proteins highlight sporozoite-specific functions. They include PF3D7_0104100 that we identified to be homologous to the prominin family, which in human has been related to a quiescent state of cancer cells. We document high levels of genetic variability for sporozoite proteins, specifically for sporozoite-specific proteins that elicit antibodies in the human host. Nevertheless, we can identify nine relatively well-conserved sporozoite proteins that elicit antibodies and that together can serve as markers for previous exposure. Our understanding of sporozoite biology benefits from identifying key pathways that are enriched during this life stage. This work can guide studies of molecular mechanisms underlying sporozoite biology and potential well-conserved targets for marker and drug development.

scholarly journals Merocyanine 540-sensitized photoinactivation of human erythrocytes parasitized by Plasmodium falciparum

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 21-24 ◽  
Author(s):  
OM Smith ◽  
SA Dolan ◽  
JA Dvorak ◽  
TE Wellems ◽  
F Sieber
Keyword(s):  
Stem Cells ◽  
Plasmodium Falciparum ◽  
Hematopoietic Stem Cells ◽  
Red Blood Cells ◽  
Human Blood ◽  
Blood Cells ◽  
Potential Usefulness ◽  
Hematopoietic Stem ◽  
Infected Blood ◽  
Merocyanine 540

The purpose of this study was to evaluate the photosensitizing dye merocyanine 540 (MC540) as a means for extracorporeal purging of Plasmodium falciparum-infected erythrocytes from human blood. Parasitized red blood cells bound more dye than nonparasitized cells, and exposure to MC540 and light under conditions that are relatively well tolerated by normal erythrocytes and normal pluripotent hematopoietic stem cells reduced the concentration of parasitized cells by as much as 1,000-fold. Cells parasitized by the chloroquine- sensitive HB3 clone and the chloroquine-resistant Dd2 clone of P falciparum were equally susceptible to MC540-sensitized photolysis. These data suggest the potential usefulness of MC540 in the purging of P falciparum-infected blood.

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