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 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 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 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 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.

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.

The use of proteomics for the identification of promising vaccine and diagnostic biomarkers in Plasmodium falciparum

Parasitology ◽  
2020 ◽  
Vol 147 (12) ◽  
pp. 1255-1262
Author(s):  
Reza Mansouri ◽  
Mohammad Ali-Hassanzadeh ◽  
Reza Shafiei ◽  
Amir Savardashtaki ◽  
Mohammadreza Karimazar ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Immune Responses ◽  
The Other ◽  
Diagnostic Biomarkers ◽  
Life Cycle Stages ◽  
Antigenic Proteins ◽  
Human Sera ◽  
Altered Proteins ◽  
Key Pathways

AbstractPlasmodium falciparum is the main cause of severe malaria in humans that can lead to death. There is growing evidence of drug-resistance in P. falciparum treatment, and the design of effective vaccines remains an ongoing strategy to control the disease. On the other hand, the recognition of specific diagnostic markers for P. falciparum can accelerate the diagnosis of this parasite in the early stages of infection. Therefore, the identification of novel antigenic proteins especially by proteomic tools is urgent for vaccination and diagnosis of P. falciparum. The proteome diversity of the life cycle stages of P. falciparum, the altered proteome of P. falciparum-infected human sera and altered proteins in P. falciparum-infected erythrocytes could be proposed as appropriate proteins for the aforementioned aims. Accordingly, this review highlights and proposes different proteins identified using proteomic approaches as promising markers in the diagnosis and vaccination of P. falciparum. It seems that most of the candidates identified in this study were able to elicit immune responses in the P. falciparum-infected hosts and they also played major roles in the life cycle, pathogenicity and key pathways of this parasite.

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