A long and winding road: The Plasmodium sporozoite's journey in the mammalian host

Sinnis, Photini; Coppi, Alida

doi:10.1016/j.parint.2007.04.002

Cited by 64 publications

(64 citation statements)

References 88 publications

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“…These interactions would be expected to be driving forces in the selection for specific extracellular proteins that underpin recognition, adherence and response to target cells. For example, Plasmodium sporozoites interact with a diverse set of host tissues -firstly salivary gland tissue in the mosquito, and subsequently tropism to hepatocytes in the liver -utilizing receptor-mediated recognition of target cells (reviewed in Sinnis and Coppi, 2007). Alveolate recognition of the environment also includes positive and negative taxis in response to gradients of nutrients, toxins, light and gravity (Eckert, 1972;Fenchel and Finlay, 1984;Francis and Hennessey, 1995;Hemmersbach et al 1999;Selbach and Kuhlmann, 1999;Cadetti et al 2000;reviewed in Echevarria et al 2014), as well as avoidance interactions with predators (Knoll et al 1991;Hamel et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Diversity of extracellular proteins during the transition from the ‘proto-apicomplexan’ alveolates to the apicomplexan obligate parasites

Templeton

Pain

2015

Parasitology

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S U M M A R YThe recent completion of high-coverage draft genome sequences for several alveolate protozoans -namely, the chromerids, Chromera velia and Vitrella brassicaformis; the perkinsid Perkinsus marinus; the apicomplexan, Gregarina niphandrodes, as well as high coverage transcriptome sequence information for several colpodellids, allows for new genome-scale comparisons across a rich landscape of apicomplexans and other alveolates. Genome annotations can now be used to help interpret fine ultrastructure and cell biology, and guide new studies to describe a variety of alveolate life strategies, such as symbiosis or free living, predation, and obligate intracellular parasitism, as well to provide foundations to dissect the evolutionary transitions between these niches. This review focuses on the attempt to identify extracellular proteins which might mediate the physical interface of cell-cell interactions within the above life strategies, aided by annotation of the repertoires of predicted surface and secreted proteins encoded within alveolate genomes. In particular, we discuss what descriptions of the predicted extracellular proteomes reveal regarding a hypothetical last common ancestor of a pre-apicomplexan alveolate -guided by ultrastructure, life strategies and phylogenetic relationships -in an attempt to understand the evolution of obligate parasitism in apicomplexans.

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Section: Introductionmentioning

confidence: 99%

Diversity of extracellular proteins during the transition from the ‘proto-apicomplexan’ alveolates to the apicomplexan obligate parasites

Templeton

Pain

2015

Parasitology

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“…Both immune individuals immunized with sporozoites and prophylactically treated with chloroquine and semiimmune patients from an area where malaria is endemic are able to recognize CSP, showing that anti-CSP immunity is necessary for protection (49). CSP binds to highly sulfated heparan sulfate proteoglycans (HSPG) on the surfaces of hepatocytes; this interaction is critical for cell invasion, arresting circulating sporozoites in the liver (45,50,51). Our heparan sulfate binding assay showed that the structural domains involved in such interactions are conserved in PvRMC-CSP.…”

Section: Discussionmentioning

confidence: 99%

Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera

et al. 2015

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dPlasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside subSaharan Africa. An effective vaccine is essential for successful control and potential eradication. A well-characterized vaccine candidate is the circumsporozoite protein (CSP). Preclinical and clinical trials have shown that both antibodies and cellular immune responses have been correlated with protection induced by immunization with CSP. On the basis of our reported approach of developing chimeric Plasmodium yoelii proteins to enhance protective efficacy, we designed PvRMC-CSP, a recombinant chimeric protein based on the P. vivax CSP (PvCSP). In this engineered protein, regions of the PvCSP predicted to contain human T cell epitopes were genetically fused to an immunodominant B cell epitope derived from the N-terminal region I and to repeat sequences representing the two types of PvCSP repeats. The chimeric protein was expressed in soluble form with high yield. As the immune response to PvCSP has been reported to be genetically restricted in the murine model, we tested the immunogenicity of PvRMC-CSP in groups of six inbred strains of mice. PvRMC-CSP was able to induce robust antibody responses in all the mouse strains tested. Synthetic peptides representing the allelic forms of the P. vivax CSP were also recognized to a similar extent regardless of the mouse strain. Furthermore, the immunization regimen induced high frequencies of multifunctional CD4؉ and CD8 ؉ PvRMC-CSP-specific T cells. The depth and breadth of the immune responses elicited suggest that immunization with PvRMC-CSP can circumvent the genetic restriction of the immune response to P. vivax CSP. Interestingly, PvRMC-CSP was also recognized by naturally acquired antibodies from individuals living in areas where malaria is endemic. These features make PvRMC-CSP a promising vaccine candidate for further development. P lasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside sub-Saharan Africa, with an estimated 2.48 billion people living in areas with risk of malaria transmission (1-4). Unlike Plasmodium falciparum, P. vivax is able to persist in a latent stage called hypnozoite within infected parenchymal liver cells. Activation of hypnozoites weeks or months after the primary infection leads to new blood stage infections, causing relapses and opportunities for further transmission (5).A vaccine targeting the P. vivax preerythrocytic stages preventing the entry of sporozoites into hepatocytes or inhibiting the liver stage development could block the production of hypnozoites. The most-characterized antigen and one of the few vaccine candidates for P. vivax tested in clinical trials is the circumsporozoite protein (CSP). CSP is an attractive target, since anti-CSP antibodies derived from naturally infected patients or from volunteers exposed to irradiated sporozoites have the ability to inhibit the infection of hepatic cells by sporozoites in vitro (6). Unlike P. ...

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“…Sporozoites must overcome natural barriers to reach their host/target cell (the hepatocyte), including circumventing the liver's sinusoidal barrier and Disse's space via Kupffer cells (Sinnis and Coppi 2007). Along with CSP, TRAP and SPECT 1 and 2, two new proteins have been recently described as they are directly involved in sporozoite cell-traversal and hepatic cell invasion: Cel-TOS and TRSP, respectively (Kaiser et al 2004b;Kariu et al 2006;Labaied et al 2007;Bergmann-Leitner et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…P. falciparum sporozoites (larvae-like structures) injected into the skin during the bite of an infected female Anopheles mosquito travel through the bloodstream to the liver during the first phase of human malaria infection where they cross the sinusoidal layer through Disse's space and Kupffer cells to invade their primary target: the hepatic cell (Sinnis and Coppi 2007). Two highly relevant proteins participating in such host-pathogen interactions have been widely studied: the circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) (Akhouri et al 2008;Rathore et al 2003); both have been shown to mediate sporozoite motility, host-cell recognition, cell traversal, binding, and entry to host cells.…”

Section: Introductionmentioning

confidence: 99%

Binding activity, structure, and immunogenicity of synthetic peptides derived from Plasmodium falciparum CelTOS and TRSP proteins

et al. 2011

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Several sporozoite proteins have been associated with Plasmodium falciparum cell traversal and hepatocyte invasion, including the cell-traversal protein for ookinetes and sporozoites (CelTOS), and thrombospondin-related sporozoite protein (TRSP). CelTOS and TRSP amino acid sequences have been finely mapped to identify regions specifically binding to HeLa and HepG2 cells, respectively. Three high-activity binding peptides (HABPs) were found in CelTOS and one HABP was found in TRSP, all of them having high α-helical structure content. These HABPs' specific binding was sensitive to HeLa and HepG2 cells' pre-treatment with heparinase I and chondroitinase ABC. Despite their similarity at three-dimensional (3D) structural level, TRSP and TRAP HABPs located in the TSR domain did not compete for the same binding sites. CelTOS and TRSP HABPs were used as a template for designing modified sequences to then be assessed in the Aotus monkey experimental model. Antibodies directed against these modified HABPs were able to recognize both the native parasite protein by immunofluorescence assay and the recombinant protein (expressed in Escherichia coli) by Western blot and ELISA assays. The results suggested that these modified HABPs could be promising targets in designing a fully effective, antimalarial vaccine.

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A long and winding road: The Plasmodium sporozoite's journey in the mammalian host

Abstract: The Plasmodium sporozoite, the infectious stage of the malaria parasite, makes a remarkable journey in its mammalian host. Here we review our current knowledge of the molecular and cellular basis of this journey, which begins in the skin and ends in the hepatocyte.

Cited by 64 publications

References 88 publications

Diversity of extracellular proteins during the transition from the ‘proto-apicomplexan’ alveolates to the apicomplexan obligate parasites

Diversity of extracellular proteins during the transition from the ‘proto-apicomplexan’ alveolates to the apicomplexan obligate parasites

Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera

Binding activity, structure, and immunogenicity of synthetic peptides derived from Plasmodium falciparum CelTOS and TRSP proteins

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