scholarly journals Malaria Transmission and Naturally Acquired Immunity to PfEMP-1

1999 ◽  
Vol 67 (12) ◽  
pp. 6369-6374 ◽  
Author(s):  
Karen P. Piper ◽  
Rhian E. Hayward ◽  
Martin J. Cox ◽  
Karen P. Day
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Membrane Protein ◽  
Malaria Transmission ◽  
Papua New Guinea ◽  
Immunoglobulin G ◽  
Acquired Immunity ◽  
Life Cycle Stages ◽  
Immune Mediated ◽  
Transmission Stage

ABSTRACT Why there are so few gametocytes (the transmission stage of malaria) in the blood of humans infected with Plasmodiumspp. is intriguing. This may be due either to reproductive restraint by the parasite or to unidentified gametocyte-specific immune-mediated clearance mechanisms. We propose another mechanism, a cross-stage immunity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1). This molecule is expressed on the surface of the erythrocyte infected with either trophozoite or early gametocyte parasites. Immunoglobulin G antibodies to PfEMP-1, expressed on both life cycle stages, were measured in residents from an area where malaria is endemic, Papua New Guinea. Anti-PfEMP-1 prevalence increased with age, mirroring the decline in both the prevalence and the density of asexual and transmission stages in erythrocytes. These data led us to propose that immunity to PfEMP-1 may influence malaria transmission by regulation of the production of gametocytes. This regulation may be achieved in two ways: (i) by controlling asexual proliferation and density and (ii) by affecting gametocyte maturation.

scholarly journals Probing Plasmodium falciparum sexual commitment at the single-cell level

2018 ◽  
Vol 3 ◽  
pp. 70 ◽  
Author(s):  
Nicolas M.B. Brancucci ◽  
Mariana De Niz ◽  
Timothy J. Straub ◽  
Deepali Ravel ◽  
Lauriane Sollelis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Single Cell ◽  
Transcriptional Profiling ◽  
Quantitative Imaging ◽  
Complex Life Cycle ◽  
Major Transitions ◽  
Transcriptional Signature ◽  
Life Cycle Stages ◽  
Parasite Populations

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign.

Overlapping antigenic repertoires of variant antigens expressed on the surface of erythrocytes infected by Plasmodium falciparum

Parasitology ◽  
1999 ◽  
Vol 119 (1) ◽  
pp. 7-17 ◽  
Author(s):  
H. A. GIHA ◽  
T. STAALSOE ◽  
D. DODOO ◽  
I. M. ELHASSAN ◽  
C. ROPER ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Malaria Transmission ◽  
Erythrocyte Membrane ◽  
Clonal Variation ◽  
Single Infection ◽  
Erythrocyte Membrane Protein ◽  
Degree Of Overlap ◽  
Eastern Sudan

Antibodies against variable antigens expressed on the surface of Plasmodium falciparum-infected erythrocytes are believed to be important for protection against malaria. A target for these antibodies is the P. falciparum erythrocyte membrane protein 1, PfEMP1, which is encoded by around 50 var genes and undergoes clonal variation. Using agglutination and mixed agglutination tests and flow cytometry to analyse the recognition of variant antigens on parasitized erythrocytes by plasma antibodies from individuals living in Daraweesh in eastern Sudan, an area of seasonal and unstable malaria transmission, we show that these antibodies recognize different variant antigens expressed by parasites of different genotype. Comparing the levels and acquisition of antibody to variant antigens in pairs of parasite isolates expressing different variant types, there is a correlation between the acquisition of antibodies to some combinations of variant antigens but not to others. These results indicate that (1) a single infection will induce the production of antibodies recognizing several variants of surface-expressed antigens, (2) the repertoire of variable antigens expressed by different parasites is overlapping and the degree of overlap differs between isolates, and (3) the expression of at least some variant antigens is genetically linked.

scholarly journals Pre-erythrocytic antibody profiles induced by controlled human malaria infections in healthy volunteers under chloroquine prophylaxis

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Philip L. Felgner ◽  
Meta Roestenberg ◽  
Li Liang ◽  
Christopher Hung ◽  
Aarti Jain ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Healthy Volunteers ◽  
Protective Immunity ◽  
Circumsporozoite Protein ◽  
Blood Stage ◽  
Asexual Blood Stage ◽  
Liver Stage ◽  
Human Malaria ◽  
Life Cycle Stages

Abstract Complete sterile protection to Plasmodium falciparum (Pf) infection mediated by pre-erythrocytic immunity can be experimentally induced under chloroquine prophylaxis, through immunization with sporozoites from infected mosquitoes' bites (CPS protocol). To characterize the profile of CPS induced antibody (Ab) responses, we developed a proteome microarray containing 809 Pf antigens showing a distinct Ab profile with recognition of antigens expressed in pre-erythrocytic life-cycle stages. In contrast, plasma from naturally exposed semi-immune individuals from Kenya was skewed toward antibody reactivity against asexual blood stage antigens. CPS-immunized and semi-immune individuals generated antibodies against 192 and 202 Pf antigens, respectively, but only 60 antigens overlapped between the two groups. Although the number of reactive antigens varied between the CPS-immunized individuals, all volunteers reacted strongly against the pre-erythrocytic antigens circumsporozoite protein (CSP) and liver stage antigen 1 (LSA1). Well classified merozoite and erythrocytic antigens were strongly reactive in semi-immune individuals but lacking in the CPS immunized group. These data show that the antibody profile of CPS-immunized and semi-immune groups have quite distinct profiles reflecting their protective immunity; antibodies from CPS immunized individuals react strongly against pre-erythrocytic while semi-immune individuals mainly react against erythrocytic antigens.

scholarly journals Probing Plasmodium falciparum sexual commitment at the single-cell level

2018 ◽  
Vol 3 ◽  
pp. 70
Author(s):  
Nicolas M.B. Brancucci ◽  
Mariana De Niz ◽  
Timothy J. Straub ◽  
Deepali Ravel ◽  
Lauriane Sollelis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Single Cell ◽  
Transcriptional Profiling ◽  
Quantitative Imaging ◽  
Complex Life Cycle ◽  
Major Transitions ◽  
Transcriptional Signature ◽  
Life Cycle Stages ◽  
Parasite Populations

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign.

scholarly journals Probing Plasmodium falciparum sexual commitment at the single-cell level

2018 ◽  
Vol 3 ◽  
pp. 70 ◽  
Author(s):  
Nicolas M.B. Brancucci ◽  
Mariana De Niz ◽  
Timothy J. Straub ◽  
Deepali Ravel ◽  
Lauriane Sollelis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Single Cell ◽  
Transcriptional Profiling ◽  
Quantitative Imaging ◽  
Complex Life Cycle ◽  
Major Transitions ◽  
Transcriptional Signature ◽  
Life Cycle Stages ◽  
Parasite Populations

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign.

scholarly journals Levels of Plasma Immunoglobulin G with Specificity against the Cysteine-Rich Interdomain Regions of a Semiconserved Plasmodium falciparum Erythrocyte Membrane Protein 1, VAR4, Predict Protection against Malarial Anemia and Febrile Episodes

2006 ◽  
Vol 74 (5) ◽  
pp. 2867-2875 ◽  
Author(s):  
John P. A. Lusingu ◽  
Anja T. R. Jensen ◽  
Lasse S. Vestergaard ◽  
Daniel T. Minja ◽  
Michael B. Dalgaard ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Immunoglobulin G ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Erythrocyte Membrane Protein ◽  
Igg Binding ◽  
Febrile Episodes

ABSTRACT Antibodies to variant surface antigen have been implicated as mediators of malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important target for these antibodies, but no study has directly linked the presence of PfEMP1 antibodies in children to protection. We measured plasma IgG levels to the cysteine-rich interdomain region 1α (CIDR1α) of VAR4 (VAR4-CIDR1α), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically for 7 months. The participants resided in Mkokola (a high-transmission village where malaria is holoendemic) or Kwamasimba (a moderate-transmission village). For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1) constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured. VAR4-CIDR1α antibodies were acquired at an earlier age in Mkokola than in Kwamasimba, but after the age of 10 years the levels were comparable in the two villages. After controlling for age and other covariates, the risk of having anemia at enrollment was reduced in VAR4-CIDR1α responders for Mkokola (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.29 to 0.88; P = 0.016) and Kwamasimba (AOR, 0.33; 95% CI, 0.16 to 0.68; P = 0.003) villages. The risk of developing malaria fever was reduced among individuals with a measurable VAR4-CIDR1α response from Mkokola village (AOR, 0.51; 95% CI, 0.29 to 0.89; P = 0.018) but not in Kwamasimba. Antibody levels to the MSP1 constructs and the control CIDR1α domain were not associated with morbidity protection. These data strengthen the concept of developing vaccines based on PfEMP1.

scholarly journals IgG Antibodies to Endothelial Protein C Receptor-Binding Cysteine-Rich Interdomain Region Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1 Are Acquired Early in Life in Individuals Exposed to Malaria

2015 ◽  
Vol 83 (8) ◽  
pp. 3096-3103 ◽  
Author(s):  
Louise Turner ◽  
Thomas Lavstsen ◽  
Bruno P. Mmbando ◽  
Christian W. Wang ◽  
Pamela A. Magistrado ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Malaria Transmission ◽  
Severe Malaria ◽  
Erythrocyte Membrane ◽  
Protein C ◽  
Endothelial Protein C Receptor ◽  
Content Type ◽  
Erythrocyte Membrane Protein ◽  
Amino Terminal

Severe malaria syndromes are precipitated byPlasmodium falciparumparasites binding to endothelial receptors on the vascular lining. This binding is mediated by members of the highly variantP. falciparumerythrocyte membrane protein 1 (PfEMP1) family. We have previously identified a subset of PfEMP1 proteins associated with severe malaria and found that the receptor for these PfEMP1 variants is endothelial protein C receptor (EPCR). The binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDR) of the subtypes α1.1 and α1.4 to α1.8. In this study, we investigated the acquisition of anti-CIDR antibodies using plasma samples collected in four study villages with different malaria transmission intensities in northeastern Tanzania during a period with a decline in malaria transmission. We show that individuals exposed to high levels of malaria transmission acquire antibodies to EPCR-binding CIDR domains early in life and that these antibodies are acquired more rapidly than antibodies to other CIDR domains. The rate by which antibodies to EPCR-binding CIDR domains are acquired in populations in areas where malaria is endemic is determined by the malaria transmission intensity, and on a population level, the antibodies are rapidly lost if transmission is interrupted. This indicates that sustained exposure is required to maintain the production of the antibodies.

scholarly journals Different Life Cycle Stages of Plasmodium falciparum Induce Contrasting Responses in Dendritic Cells

2019 ◽  
Vol 10 ◽  
Author(s):  
Xi Zen Yap ◽  
Rachel J. Lundie ◽  
Gaoqian Feng ◽  
Joanne Pooley ◽  
James G. Beeson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Life Cycle ◽  
Life Cycle Stages

scholarly journals A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhenghui Huang ◽  
Ruoxi Li ◽  
Tongke Tang ◽  
Dazheng Ling ◽  
Manjiong Wang ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Multidrug Resistance ◽  
Histone Deacetylase ◽  
Malaria Parasites ◽  
Histone Deacetylase 1 ◽  
Life Cycle Stages ◽  
Deacetylase Inhibitor ◽  
Transcriptomic Changes ◽  
Artemisinin Combination Therapies

AbstractAlthough artemisinin combination therapies have succeeded in reducing the global burden of malaria, multidrug resistance of the deadliest malaria parasite, Plasmodium falciparum, is emerging worldwide. Innovative antimalarial drugs that kill all life-cycle stages of malaria parasites are urgently needed. Here, we report the discovery of the compound JX21108 with broad antiplasmodial activity against multiple life-cycle stages of malaria parasites. JX21108 was developed from chemical optimization of quisinostat, a histone deacetylase inhibitor. We identified P. falciparum histone deacetylase 1 (PfHDAC1), an epigenetic regulator essential for parasite growth and invasion, as a molecular target of JX21108. PfHDAC1 knockdown leads to the downregulation of essential parasite genes, which is highly consistent with the transcriptomic changes induced by JX21108 treatment. Collectively, our data support that PfHDAC1 is a potential drug target for overcoming multidrug resistance and that JX21108 treats malaria and blocks parasite transmission simultaneously.

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