Host cell manipulation by the human pathogen Toxoplasma gondii

Toxoplasma gondii is an obligate intracellular parasite that can infect virtually any nucleated cell. During invasion Toxoplasma creates the parasitophorous vacuole, a subcellular compartment that acts as an interface between the parasite and host, and serves as a platform for modulation of host cell functions that support parasite replication and infection. Spatial reorganization of host organelles and cytoskeleton around the parasitophorous vacuole are observed following entry, and recent evidence suggests this interior redecorating promotes parasite nutrient acquisition. New findings also reveal that Toxoplasma manipulates host signaling pathways by deploying parasite kinases and a phosphatase, including at least two that infiltrate the host nucleus. Toxoplasma infection additionally controls several cellular pathways to establish an anti-apoptotic environment, and subverts immune cells as a conduit for dissemination. In this review we discuss these recent developments in understanding how Toxoplasma achieves widespread success as a human and animal parasite by manipulating its host.     

Hemagglutination of neuraminidase-treated human erythrocytes by Leishmania enriettii infected guinea-pig sera.

Sera from guinea-pigs infected with the protozoan parasite Leishmania enriettii showed higher hemagglutination (HA) titres for neuraminidase treated human erythrocytes than those of normal guinea-pig sera. This HA activity was associated mostly with the 19S fraction of the immune serum and could be absorbed out with an antigenic fraction of the parasite membrane. Antigenic determinants involved in this HA reaction consisted of, at least, beta-D-galactosyl or lactosyl residues.     

Phospholipid composition of Dipylidium caninum

The phospholipid composition of Dipylidium caninum has been studied. Chloroform-methanol-soluble fraction amounted to 2.4% and phospholipids to 0.5% of the wet weight of the parasite. Phosphatidyl choline and phosphatidyl ethanolamine represented the bulk of the phospholipids, whereas phosphatidyl serine, phosphatidyl inositol, lysolecithin and lysophosphatidyl ethanolamine were present in minor amounts. Sulfatides were also identified in this parasite.     

Phyletic affinities among Polystomatidae (Monogenea)]

The chaetotaxy and ciliated cells in two Monogenean larvae of marine fishes are described for the first time: a Monopisthocotylea Diplectanum aequans (Wagener, 1857) Diesing, 1858 parasite of Dicentrarchus Labrax (L) and a Polyopisthocotylea, Microcotyle mormyri Lorenz, 1878 parasite of Pagellus mormyrus (L). A comparative study with the known larvae shows evidence of two larval types in the Monogenea of fishes, related to the two great phyla of the class: the Monopisthocoytylea and Polyopisthocotylea. The Polystomatidae, Monogenea from Amphibia and Chelonia, belong to the Polyopisthocotylea on account of their larval chaetotaxy. But the proximity of the Polystomatidae with the Tetraonchidae, within the Polyonchoinea Bychowsky, 1975 is not confirmed.     

Arginase expression in peritoneal macrophages and increase in circulating polyamine levels in mice infected with Schistosoma mansoni

We investigated the nitric oxide (NO) synthase and arginase pathways in resident peritoneal macrophages of mice infected with the tropical parasite Schistosoma mansoni. The two enzymes may have opposite effects, insofar as NO may be involved in the killing of the parasite whereas arginase may stimulate parasite growth via polyamine synthesis. We determined the effects of the infection on the expression and activity of the two enzymes in macrophages, before and after cytokine activation. Cells from infected mice expressed the hepatic type I arginase, whereas in control cells, the enzyme was expressed only after cytokine activation, as were NO synthase II and type II arginase in both groups of cells. Moreover, we found that in infected mice, arginase expression in macrophages was associated with a ten fold increase in the concentration of circulating ornithine-derived polyamines. This may be of pathological importance, since parasitic helminths are though to be dependent on their hosts for the uptake and interconversion of polyamines. Received 13 March 2001; received after revision 4 May 2001; accepted 7 June 2001     

Interaction of benznidazole reactive metabolites with nuclear and kinetoplastic DNA, proteins and lipids from Trypanosoma cruzi

Epimastigotes of Trypanosoma cruzi (Tulahuen strain Tul 0 stock) biotransform benznidazole (N-benzyl-2-nitro-1-imidazole acetamide) to reactive metabolites that bind covalently to DNA, proteins and lipids of the parasite. These effects might be related to the trypanocidal action of benznidazole, a chemotherapeutic agent against Chagas' disease.     

Encapsulation ofPsorospermium haeckeli by the haemocytes ofAstacus leptodactylus

Summary Psorospermium haeckeli, a parasite of freshwater crayfish, has sometimes been observed encapsulated within the tissues ofAstacus leptodactylus. This observation does not agree with earlier reports. The lack of tolerance is discussed in relation to variations affecting either the parasite or its host.     

Phospholipid composition ofDipylidium caninum

Summary The phospholipid composition ofDipylidium caninum has been studied. Chloroform-methanol-soluble fraction amounted to 2.4% and phospholipids to 0.5% of the wet weight of the parasite. Phosphatidyl choline and phosphatidyl ethanolamine represented the bulk of the phospholipids, whereas phosphatidyl serine, phosphatidyl inositol, lysolecithin and lysophosphatidyl ethanolamine were present in minor amounts. Sulfatides were also identified in this parasite.     

Interaction of benznidazole reactive metabolites with nuclear and kinetoplastic DNA,proteins and lipids fromTrypanosoma cruzi

Summary Epimastigotes ofTrypanosoma cruzi (Tulahuen strain Tul 0 stock) biotransform benznidazole (N-benzyl-2-nitro-1-imidazone acetamide) to reactive metabolites that bind covalently to DNA, proteins and lipids of the parasite. These effects might be related to the trypanocidal action of benznidazole, a chemotherapeutic agent against Chagas' disease.     

Membrane-shed vesicles from the parasite <Emphasis Type="Italic">Trichomonas vaginalis</Emphasis>: characterization and their association with cell interaction

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract, where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Despite the serious consequences associated with trichomoniasis disease, little is known about parasite or host factors involved in attachment of the parasite-to-host epithelial cells. Here, we report the identification of microvesicle-like structures (MVs) released by T. vaginalis. MVs are considered universal transport vehicles for intercellular communication as they can incorporate peptides, proteins, lipids, miRNA, and mRNA, all of which can be transferred to target cells through receptor–ligand interactions, fusion with the cell membrane, and delivery of a functional cargo to the cytoplasm of the target cell. In the present study, we demonstrated that T. vaginalis release MVs from the plasma and the flagellar membranes of the parasite. We performed proteomic profiling of these structures demonstrating that they possess physical characteristics similar to mammalian extracellular vesicles and might be selectively charged with specific protein content. In addition, we demonstrated that viable T. vaginalis parasites release large vesicles (LVs), membrane structures larger than 1 µm that are able to interact with other parasites and with the host cell. Finally, we show that both populations of vesicles present on the surface of T vaginalis are induced in the presence of host cells, consistent with a role in modulating cell interactions.     

Chromatographic evidence for the synthesis of possible sleep-mediators inTrypanosoma brucei gambiense

Résumé Les trypanosomes ont converti les substratsl-tryptophan etdl-5-hydroxytryptophan en métabolites tryptophol (indole-3-éthanol) et 5-hydroxytryptophol, deux composés qui produisent le sommeil chez la souris et le poussin. Les effets possibles de ces composés soporifiques chez un homme infecté par ce parasite et leur rôle dans le métabolisme du parasite, sont discutés.

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Supported in part by a Research Corporation grant from the Brown-Hazen fund.     

Mechanisms of cellular invasion by intracellular parasites

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world’s population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite–host cell interactions, forming the basis of the parasite’s cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.     

Molecular diagnosis of parasites

Summary New developments in molecular biology have generated exciting possibilities for improved diagnosis of parasitic diseases. Through gene clonign and expression and peptide synthesis, defined parasite antigens can be produced in vitro for use in serodiagnosis, while nuclear hybridization techniques offer a vastly improved approach to identification of parasites in the tissue specimens of infected hosts as a means of diagnosis. Furthermore, the advent of the polymerase chain reaction technique has made it possible to increase the sensitivity of nuclear hybridization techniques, through amplification of target DNA sequences of the parasites in test material, by in situ synthesis of these sequences prior to hybridization with the diagnostic probe. Finally, through the use of monoclonal antibody technology, it is possible to design highly specific and sensitive serological assays, as well as assays for parasite antigen detection in tissue fluids and in the excreta of infected hosts, as a means of diagnosis.     

Molecular diagnosis of parasites

New developments in molecular biology have generated exciting possibilities for improved diagnosis of parasitic diseases. Through gene cloning and expression and peptide synthesis, defined parasite antigens can be produced in vitro for use in serodiagnosis, while nuclear hybridization techniques offer a vastly improved approach to identification of parasites in the tissue specimens of infected hosts as a means of diagnosis. Furthermore, the advent of the polymerase chain reaction technique has made it possible to increase the sensitivity of nuclear hybridization techniques, through amplification of target DNA sequences of the parasites in test material, by in situ synthesis of these sequences prior to hybridization with the diagnostic probe. Finally, through the use of monoclonal antibody technology, it is possible to design highly specific and sensitive serological assays, as well as assays for parasite antigen detection in tissue fluids and in the excreta of infected hosts, as a means of diagnosis.     

Observation of Schistosoma mansoni by scanning electron microscopy]

The integumental surface of adult Schistosoma mansoni was studied by scanning electron microscopy (SEM) at 220 to 10,000 magnifications. SEM shows certain basic features such as spines in the oral sucker and the acetabulum which may facilitate rasping and attachment of the parasite to stay in the bloodstream of the definitive host. It seems likely that SEM visualization will be a means for differentiation some species of the genus Schistosoma.     

Our impasse in developing a malaria vaccine

Malaria presents a challenge to world health that to date has been beyond the abilities of researchers to conquer. This critique presents some of the strategies employed by the parasite to overcome immunity and the immunological challenges that we face to develop vaccines. A conclusion is that a vaccine must identify novel antigens or epitopes that are not normally immunogenic and which are therefore not under immune pressure and most likely to be conserved between different strains. Such antigens are most likely to be targets of cellular immunity. The case for a whole parasite blood stage vaccine is presented based on these premises.     

Permissivity of the rat (Rattus rattus) of Guadeloupe with regard to Schistosoma mansoni and evidence for migration of adult schistosomes to the lungs]

In contrast to the laboratory Rat, the Rat (Rattus rattus) of Guadeloupe is a favorable host for the life cycle of S. mansoni: the parasite population is maintained at a high level (between 8 and 16% in this host until the 16th week and reproduces normally). The evolution of the parasitose is marked, shortly after the 8th week, by a transfer of schistosomes from the liver to the lungs.     

Evolution and ecological correlates of uniparental reproduction in freshwater snails

We review the spatial and temporal correlates of uniparental reproduction in freshwater snails as they pertain to the ecological hypotheses for the maintenance of biparental sex. The biogeographic evidence from two species (Potamopyrgus antipodarum andBulinus truncatus) presently supports the Red Queen hypothesis that biparental reproduction is selected as a way to reduce the risk to progeny of parasite attack. Uniparental reproduction in these species is associated with low levels of infection by parasites (castrating digenetic trematodes), suggesting that parthenogenesis or self-fertilization can replace cross-fertilization when the risk of infection is low. In addition, inB. truncatus, the opportunity for cross-fertilization coincides with the season in which parasite attack is highest. In a third species (Campeloma decisum), parthenogenetic reproduction is correlated with latitude and the presence of a non-castrating trematode that may prevent cross-fertilization; these patterns suggest that parthenogenesis has been selected as a mechanism to assure reproduction. Finally, we discuss the spotty taxonomic distribution of parthenogenetic species.     

Effect of injection of a phosphorylcholine-containing compound from Nippostrongylus brasiliensis on the infestation of the rat by this parasite]

Rats were injected intradermally with the purified phosphorycholine bearing component of the nematode Nippostrongylus brasiliensis. Eight days later they were experimentally infected with 1 X 10(3) infective larvae of the parasite. Compared to the non injected controls we showed a significant decrease in the number of adult worms able to be established in the small intestine. This protective effect seems to be due at least partly to a phenomenom being located between the skin and the lungs of the rats.