Developmental-stage-specific triacylglycerol biosynthesis, degradation and trafficking as lipid bodies in Plasmodium falciparum-infected erythrocytes

N. M. Q. Palacpac

doi:10.1242/jcs.00988

Food vacuole-associated lipid bodies and heterogeneous lipid environments in the malaria parasite, Plasmodium falciparum

Molecular Microbiology ◽

10.1111/j.1365-2958.2004.04284.x ◽

2004 ◽

Vol 54 (1) ◽

pp. 109-122 ◽

Cited By ~ 108

Author(s):

Katherine E. Jackson ◽

Nectarios Klonis ◽

David J. P. Ferguson ◽

Akinola Adisa ◽

Con Dogovski ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Parasite ◽

Food Vacuole ◽

Lipid Bodies ◽

Parasite Plasmodium ◽

Parasite Plasmodium Falciparum

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Phagocytosis of Plasmodium falciparum-infected human red blood cells by human monocytes: involvement of immune and nonimmune determinants and dependence on parasite developmental stage

Blood ◽

10.1182/blood.v80.3.801.801 ◽

1992 ◽

Vol 80 (3) ◽

pp. 801-808 ◽

Cited By ~ 88

Author(s):

F Turrini ◽

H Ginsburg ◽

F Bussolino ◽

GP Pescarmona ◽

MV Serra ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Blood Cell ◽

Developmental Stage ◽

Red Blood Cell ◽

Immunoglobulin G ◽

Blood Cells ◽

Protein A ◽

Human Monocytes ◽

Human Red Blood Cells ◽

Igg Binding

Abstract The stage-dependent phagocytosis of Plasmodium falciparum-infected erythrocytes (IRBC) opsonized with nonimmune serum has been investigated. An average of 2.9 red blood cell (RBC) harboring ring- forms (RIRBC) and 7.5 RBC infected with trophozoites (TIRBC) or schizonts (SIRBC) were ingested per monocyte, in comparison with 0.8 noninfected RBC (NRBC) or 5 RBC oxidatively damaged with diamide. Abrogation of generation of complement component C3b or blockage of its binding to the phagocyte inhibited phagocytosis of RIRBC by 78% to 95% and of TIRBC by 25% to 50%. Blockage of immunoglobulin G (IgG) binding reduced phagocytosis of both RIRBC and TIRBC nonsignificantly by 14%. Preincubation of monocytes with phosphatidylserine (PS)-containing liposomes reduced phagocytosis of TIRBC by 22%, but had little effect on RIRBC. Residual, noncomplement, non-IgG-, and non-PS-dependent phagocytosis amounted to 6% to 18% of total phagocytosis in RIRBC and TIRBC, respectively. RIRBC bound 2.5 times more protein A and 3.1 times more anti-C3c (a stable derivative of C3b) antibodies, and TIRBC bound 20 times more protein A and 6.8 times more anti-C3c antibodies than NRBC. Phagocytosis of oxidatively damaged RBC and RIRBC are similar, whereas a higher portion of phagocytosis appears to be noncomplement- dependent and PS-suppressible in TIRBC. It is concluded that RIRBC generate recognition signals similar to those present in oxidatively damaged or senescent RBC. Extensive membrane modifications in TIRBC produce additional, hitherto undefined signals that induce much higher and qualitatively distinct phagocytosis.

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Cyclical Regression Covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasite Plasmodium falciparum

10.1101/2020.04.17.044552 ◽

2020 ◽

Author(s):

Gabriel J. Foster ◽

Katrina Button-Simons ◽

Katelyn Vendrely ◽

Jeanne Romero-Severson ◽

Michael T. Ferdig

Keyword(s):

Gene Expression ◽

Drug Resistance ◽

Plasmodium Falciparum ◽

Developmental Stage ◽

Drug Response ◽

Type I ◽

Data Set ◽

Blood Samples ◽

Development Cycle

AbstractBackgroundThe cyclical nature of parasite gene expression in the intraerythrocytic development cycle (IDC) in human blood confounds the accurate detection of specific transcriptional differences due to drug resistance in Plasmodium falciparum. Here, we propose the use of cyclical regression covariates to eliminate the major confounding of developmentally driven transcriptional changes with changes due to drug response. We show that elimination of this confounding can reduce both Type I and Type II errors, and demonstrate the effect of approach on real data.ResultsWe apply this method to two publicly available datasets, and demonstrate its ability to reduce the potential confounding of differences in expression due the species-specific intraerythrocytic development cycle from strain-specific differences in drug response. We show that the application of cyclical regression covariates has minimal impact on the pool of transcripts identified as significantly different in a dataset generated from single timepoint clinical blood samples with low variance for developmental stage and a profound impact on another clinical data set with more variance among the samples for developmental stage.ConclusionsCyclical regression covariates have immediate application to studies where in-vitro synchronization of all samples to the same developmental timepoint is not feasible, primarily parasite transcriptome sequencing direct from clinical blood samples, a widely used approach to frontline detection of emerging drug resistance.

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Phagocytosis of Plasmodium falciparum-infected human red blood cells by human monocytes: involvement of immune and nonimmune determinants and dependence on parasite developmental stage

Blood ◽

10.1182/blood.v80.3.801.bloodjournal803801 ◽

1992 ◽

Vol 80 (3) ◽

pp. 801-808 ◽

Cited By ~ 1

Author(s):

F Turrini ◽

H Ginsburg ◽

F Bussolino ◽

GP Pescarmona ◽

MV Serra ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Blood Cell ◽

Developmental Stage ◽

Red Blood Cell ◽

Immunoglobulin G ◽

Blood Cells ◽

Protein A ◽

Human Monocytes ◽

Human Red Blood Cells ◽

Igg Binding

The stage-dependent phagocytosis of Plasmodium falciparum-infected erythrocytes (IRBC) opsonized with nonimmune serum has been investigated. An average of 2.9 red blood cell (RBC) harboring ring- forms (RIRBC) and 7.5 RBC infected with trophozoites (TIRBC) or schizonts (SIRBC) were ingested per monocyte, in comparison with 0.8 noninfected RBC (NRBC) or 5 RBC oxidatively damaged with diamide. Abrogation of generation of complement component C3b or blockage of its binding to the phagocyte inhibited phagocytosis of RIRBC by 78% to 95% and of TIRBC by 25% to 50%. Blockage of immunoglobulin G (IgG) binding reduced phagocytosis of both RIRBC and TIRBC nonsignificantly by 14%. Preincubation of monocytes with phosphatidylserine (PS)-containing liposomes reduced phagocytosis of TIRBC by 22%, but had little effect on RIRBC. Residual, noncomplement, non-IgG-, and non-PS-dependent phagocytosis amounted to 6% to 18% of total phagocytosis in RIRBC and TIRBC, respectively. RIRBC bound 2.5 times more protein A and 3.1 times more anti-C3c (a stable derivative of C3b) antibodies, and TIRBC bound 20 times more protein A and 6.8 times more anti-C3c antibodies than NRBC. Phagocytosis of oxidatively damaged RBC and RIRBC are similar, whereas a higher portion of phagocytosis appears to be noncomplement- dependent and PS-suppressible in TIRBC. It is concluded that RIRBC generate recognition signals similar to those present in oxidatively damaged or senescent RBC. Extensive membrane modifications in TIRBC produce additional, hitherto undefined signals that induce much higher and qualitatively distinct phagocytosis.

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

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162132 ◽

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).

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