Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage

Soni, Rani; Sharma, Devesh; Rai, Praveen; Sharma, Bhaskar; Bhatt, Tarun Kumar

doi:10.3389/fimmu.2017.00349

Cited by 15 publications

(12 citation statements)

References 163 publications

(179 reference statements)

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“…The parasites use hemoglobin as a precursor of amino acid synthesis [29]. Hemoglobin is degraded to the toxic product called hematin then converts to a structural compound called hemozoin to avoid the reactive oxygen species [30,31].…”

Section: Discussionmentioning

confidence: 99%

In-Depth Biological Alteration Analysis of Plasmodium Knowelsi-Infected Red Blood Cells Using A Non-Invasive Optical Imaging Technique

Firdaus

Muh

Park

et al. 2021

Preprint

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Background Imaging techniques are commonly used for understanding disease mechanisms and their biological features in such a microenvironment of the cell. In recent work, the understanding of parasite biology of malaria Plasmodium knowlesi was compiled from functional in vitro and imaging analysis using serial block-face scanning electron microscopy (SEM). Sample fixation during SEM analysis possibly makes the parasite membrane destruction. Methods In this study, we used a non-invasive optical technique, tomography, to explore the biological changes during the development of infected red blood cells (RBCs) by P. knowlesi. The commercial common-path diffraction optical tomography was used to measure individual infected RBCs' three-dimensional refractive index tomogram without an additional dyeing agent. Results We simultaneously examined structural, chemical, and physical modification by a parasite inside of host RBCs. The results had similar patterns with previous studies using SEM and other parasites such as P. falciparum and Babesia. Interestingly we found that P. knowlesi did not use hemoglobin as much as P. falciparum as a source of nutrition. Conclusions This tomography technique opens new ways to study the pathophysiology of malaria parasites more efficiently and is considered a promising tool for studying each Plasmodium species more in-depth.

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Section: Discussionmentioning

confidence: 99%

In-Depth Biological Alteration Analysis of Plasmodium Knowelsi-Infected Red Blood Cells Using A Non-Invasive Optical Imaging Technique

Firdaus

Muh

Park

et al. 2021

Preprint

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“…So, components of calcium signaling are considered for therapeutic interventions. [62] The malaria RTS,S/AS01 vaccine uses the CSP protein as a target antigen against malaria. [57] In earlier stages of vaccine development, higher concentrations of antibodies against CSP were observed on the day of the challenge.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Gene Expression Profiles to study Malaria Vaccine Dose Efficacy & Immune Response Modulation

Dey

Kaur²,

Brodsky³

et al. 2021

Preprint

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Malaria is a life-threatening disease, and the Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of the different vaccination doses on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on 275 and 583 samples collected from the GEO datasets. At first, exploratory data analysis based Principal component analysis (PCA) shown the distinct pattern of different doses. Subsequently, differential gene expression analysis using edgeR revealed the significantly (FDR <0.005) 158 down-regulated and 61 upregulated genes between control vs. Controlled Human Malaria Infection (CHMI) samples. Further, enrichment analysis of significant genes using Annotation and GAGE tools delineate the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc.,genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight to the dual role of cytokine responses in malaria pathogenesis and variations in their expression patterns after various doses of vaccination involved in protection.

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“…Kinase signaling has been highlighted in the regulation of different biological events involved in target cell-pathogen interactions. (17,18) Activation of signaling pathways during the initial parasite-host cell interface stage promotes T. cruzi entry by cytoskeleton-dependent or -independent processes. (5) FAK, which is involved in cytoskeleton regulation, (19) is activated during T. cruzi cardiomyocyte invasion.…”

Section: Discussionmentioning

confidence: 99%

Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion

Melo

Coutinho

Pereira

2020

Mem. Inst. Oswaldo Cruz

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BACKGROUND Trypanosoma cruzi, the etiologic agent of Chagas disease, is capable of triggering different signaling pathways that modulate its internalisation in mammalian cells. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, has been demonstrated as a mechanism of T. cruzi invasion in cardiomyocytes. Since the involved cell surface receptors are not yet known, we evaluated whether heparan sulfate proteoglycans (HSPG), a molecule involved in T. cruzi recognition and in the regulation of multiple signaling pathways, are able to trigger the FAK signaling pathway during T. cruzi invasion.METHODS To investigate the role of HSPG in the regulation of the FAK signaling pathway during trypomastigote entry, we performed heparan sulfate (HS) depletion from the cardiomyocyte surface by treatment with heparinase I or p-nitrophenylβ-D-xylopyranoside (p-n-xyloside), which abolishes glycosaminoglycan (GAG) attachment to the proteoglycan core protein.Wild-type (CHO-k1) and GAG-deficient Chinese hamster ovary cells (CHO-745) were also used as an approach to evaluate the participation of the HSPG-FAK signaling pathway. FAK activation (FAK Tyr 397 ) and spatial distribution were analysed by immunoblotting and indirect immunofluorescence, respectively.FINDINGS HS depletion from the cardiomyocyte surface inhibited FAK activation by T. cruzi. Cardiomyocyte treatment with heparinase I or p-n-xyloside resulted in 34% and 28% FAK phosphorylation level decreases, respectively. The experiments with the CHO cells corroborated the role of HSPG as a FAK activation mediator. T. cruzi infection did not stimulate FAK phosphorylation in CHO-745 cells, leading to a 36% reduction in parasite invasion. FAK inhibition due to the PF573228 treatment also impaired T. cruzi entry in CHO-k1 cells.MAIN CONCLUSION Jointly, our data demonstrate that HSPG is a key molecule in the FAK signaling pathway activation, regulating T. cruzi entry.

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Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage

Cited by 15 publications

References 163 publications

In-Depth Biological Alteration Analysis of Plasmodium Knowelsi-Infected Red Blood Cells Using A Non-Invasive Optical Imaging Technique

In-Depth Biological Alteration Analysis of Plasmodium Knowelsi-Infected Red Blood Cells Using A Non-Invasive Optical Imaging Technique

Analysis of Gene Expression Profiles to study Malaria Vaccine Dose Efficacy & Immune Response Modulation

Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion

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