Interaction between the Intermediate Host of Schistosomiasis in Brazil Biomphalaria glabrata (Planorbidae) and a Possible Competitor Melanoides tuberculata (Thiaridae): I. Laboratory Experiments

The biological control of Biomphalaria glabrata, intermediate host of Schistosoma mansoni, is one the accepted options to fight schistosomiasis. One of the most promising candidates to control B. glabrata is the snail Melanoides tuberculata, a potential competitor. However, the mechanisms of interaction between the two species are not clear. Our objective is to determine if M. tuberculata indeed compete with B. glabrata, using two laboratory experiments. In Experiment 1, we tested the effect of the presence of M. tuberculata on the fecundity and mortality rates of B. glabrata. In Experiment 2, we tested if there was a direct or indirect interaction between the two species. In Experiment 1, M. tuberculata was eliminated after the peak in reproductive activity of B. glabrata. In Experiment 2, B. glabrata produced more egg masses when raised with M. tuberculata. The conditions leading to this unexpected positive effect of M. tuberculata on the fecundity of B. glabrata need further clarification, but emphasize that detailed studies of the interaction between these species in the conditions of the local environment should be considered.

Toxoplasma gondii infection induces lipid metabolism alterations in the murine host

Host lipids have been implicated in the pathogenesis of Toxoplasma gondiiinfection. To determine if Toxoplasmainfection influences the lipid status in the normal host, we assessed serum lipids of Swiss-Webster mice during infection with the BGD-1 strain (type-2) at a series of time points. Mice were bled at days zero and 42 post-infection, and subgroups were additionally bled on alternating weeks (model 1), or sacrificed at days zero, 14 and 42 (model 2) for the measurement of total cholesterol (Chl), high density lipoproteins (HDL), low density lipoproteins (LDL) and triglycerides and adiponectin. At day 42, brains were harvested for cyst enumeration. A significant decrease (p = 0.02) in HDL and total Chl was first noted in infected vs. control mice at day 14 and persisted to day 42 (p = 0.013). Conversely, LDL was unaltered until day 42, when it increased (p = 0.043). Serum LDL levels at day 42 correlated only with cyst counts of above 300 (found in 44% mice), while the change in HDL between days zero and 42 correlated with both the overall mean cyst count (p = 0.041) and cyst counts above 300 (p = 0.044). Calculated per cyst, this decrease in HDL in individual animals ranged from 0.1-17 µmol/L, with a mean of 2.43 ± 4.14 µmol/L. Serum adiponectin levels remained similar between infected and control mice throughout the experiment.

What new cell biology findings could bring to therapeutics: is it time for a phenome-project in Toxoplasma gondii?

"If you know the enemy and know yourself, you need not fear the result of a hundred battles. If you know yourself but not the enemy, for every victory gained you will also suffer a defeat" (SunTzu the Art of War, 544-496 BC). Although written for the managing of conflicts and winning clear victories, this basic guideline can be directly transferred to our battle against apicomplexan parasites and how to focus future basic research in order to transfer the gained knowledge to a therapeutic intervention stratey. Over the last two decades the establishment of several key-technologies, by different groups working on Toxoplasma gondii, made this important human pathogen accessible to modern approaches in molecular cell biology. In fact more and more researchers get attracted to this easy accessible model organism to study specific biological questions, unique to apicomplexans. This fascinating, unique biology might provide us with new therapeutic options in our battle against apicomplexan parasites by finding its Achilles' heel. In this article we argue that in the absence of a powerful high throughput technology for the characterisation of essential gene of interests a coordinated effort should be undertaken to convert our knowledge of the genome into one of the phenome.

Veterinary vaccines against Toxoplasma gondii

Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.

CD40, autophagy and Toxoplasma gondii

Toxoplasmagondii represents a pathogen that survives within host cells by preventing the endosomal-lysosomal compartments from fusing with the parasitophorous vacuoles. The dogma had been that the non-fusogenic nature of these vacuoles is irreversible. Recent studies revealed that this dogma is not correct. Cell-mediated immunity through CD40 re-routes the parasitophorous vacuoles to the lysosomal compartment by a process called autophagy. Autophagosome formation around the parasitophorous vacuole results in killing of the T. gondii. CD40-induced autophagy likely contributes to resistance against T. gondii particularly in neural tissue.

Host immune response to Toxoplasma gondii and Ascaris lumbricoides in a highly endemic area: evidence of parasite co-immunomodulation properties influencing the outcome of both infections

Toxoplasmosis and ascaridiasis evoke polar Th-1 and Th-2 host immune responses, respectively. A study to investigate the specific cytokine profile production by in vitro cultures of peripheral blood mononuclear cells from individuals living under precarious sanitary conditions in a highly endemic area for the parasites Toxoplasma gondii and Ascaris lumbricoides was conducted. High levels of both IFN-³ (Th-1) and IL-13 (Th-2) were observed in groups of co-infected individuals presenting toxoplasmic ocular lesions. Significantly lower IL-10 and TGF-² levels were produced by co-infected individuals in comparison with groups of individuals not infected with A. lumbricoides and either positive or negative for T. gondii living under good sanitary conditions (control groups). The possible influence of co-parasitism on the clinical presentation of ocular toxoplasmosis is discussed.

Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors - how to make a dream come true

One hundred years ago, Carlos Chagas discovered a new disease, the American trypanosomiasis. Chagas and co-workers later characterised the disease's common manifestation, chronic cardiomyopathy, and suggested that parasitic persistence coupled with inflammation was the key underlying pathogenic mechanism. Better comprehension of the molecular mechanisms leading to clinical heart afflictions is a prerequisite to developing new therapies that ameliorate inflammation and improve heart function without hampering parasite control. Here, we review recent data showing that distinct cell adhesion molecules, chemokines and chemokine receptors participate in anti-parasite immunity and/or detrimental leukocyte trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors may be attractive therapeutic targets aiming to regain homeostatic balance in parasite/host interaction thereby improving prognosis, supporting that it is becoming a non-phantasious proposal.

Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for chronic Chagas disease

The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease.T-helper (Th)1 and interleukin (IL)-10Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively orvice versa, depending on the T. cruziantigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ) treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruziresults from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

Interaction between Tephritidae (Insecta, Diptera) and plants of the family Asteraceae: new host and distribution records for the state of Rio Grande do Sul, Brazil

Twenty species of Tephritidae (Diptera) are recorded in association with capitula of plants in the family Asteraceae. The Tephritidae genus Tetreuarestais registered for Rio Grande do Sul for the first time. Five species of Tephritidae are newly recorded for Rio Grande do Sul, and new hosts are recorded for the following fly species: Dioxyna chilensis (Macquart), Plaumannimyia dolores (Hering), Plaumannimyia imitatrix (Hering), Plaumannimyia miseta(Hering), Plaumannimyia pallensHering, Tomoplagia incompleta (Williston), Tomoplagia matzenbacheriPrado, Norrbom & Lewinsohn, Tomoplagia reimoseriHendel, Xanthaciura biocellata(Thomson) and Xanthaciura chrysura(Thomson).

Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI) maintained by Th1 lymphocytes and IFN-T FACE="Symbol">gt>. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host). Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

Control of the adrenocortical cell cycle: interaction between FGF2 and ACTH

FGF2 elicits a strong mitogenic response in the mouse Y-1 adrenocortical tumor cell line, that includes a rapid and transient activation of the ERK-MAPK cascade and induction of the c-Fos protein. ACTH, itself a very weak mitogen, blocks the mitogenic response effect of FGF2 in the early and middle G1 phase, keeping both ERK-MAPK activation and c-Fos induction at maximal levels. Probing the mitogenic response of Y-1 cells to FGF2 with ACTH is likely to uncover reactions underlying the effects of this hormone on adrenocortical cell growth.

Lack of evidence for superantigen activity of Toxoplasma gondii towards human T cells

Toxoplasma gondii is an obligatory intracellular parasite whose life cycle may include man as an intermediate host. More than 500 million people are infected with this parasite worldwide. It has been previously reported that T. gondii contains a superantigen activity. The purpose of the present study was to determine if the putative superantigen activity of T. gondii would manifest towards human T cells. Peripheral blood mononuclear cells (PBMC) from individuals with no previous contact with the parasite were evaluated for proliferation as well as specific Vß expansion after exposure to Toxoplasma antigens. Likewise, PBMC from individuals with the congenital infection were evaluated for putative Vß family deletions in their T cell repertoire. We also evaluated, over a period of one year, the PBMC proliferation pattern in response to Toxoplasma antigens in patients with recently acquired infection. Some degree of proliferation in response to T. gondii was observed in the PBMC from individuals never exposed to the parasite, accompanied by specific Vß expansion, suggesting a superantigen effect. However, we found no specific deletion of Vß (or Valpha) families in the blood of congenitally infected individuals. Furthermore, PBMC from recently infected individuals followed up over a period of one year did not present a reduction of the Vß families that were originally expanded in response to the parasite antigens. Taken together, our data suggest that T. gondii does not have a strong superantigen activity on human T cells.

Correlation of mixed lymphocyte culture with chronic graft-versus-host disease following allogeneic stem cell transplantation

The purpose of the present study was to evaluate the mixed lymphocyte culture as a predictive assay of acute and chronic graft-versus-host disease (GVHD). We studied 153 patients who received a first bone marrow transplantation from human leukocyte antigen-identical siblings. Acute GVHD was observed in 26 of 128 (20.3%) patients evaluated and chronic GVHD occurred in 60 of 114 (52.6%). One-way mixed lymphocyte culture (MLC) assays were performed by the standard method. MLC results are reported as the relative response (RR) from donor against patient cells. The responses ranged from -47.0 to 40.7%, with a median of 0.5%. The Kaplan-Meier probability of developing GVHD was determined for patients with positive and negative MLC. There was no significant difference in incidence of acute GVHD between the groups studied. However, the incidence of chronic GVHD was higher in recipients with RR >4.5% than in those with RR <=4.5%. The Cox Proportional Hazards model was used to examine the effect of MLC levels on incidence of chronic GVHD, while adjusting for the potential confounding effect of others suspected or observed risk factors. The relative risk of chronic GVHD was 2.5 for patients with positive MLC (RR >4.5%), 2.9 for those who received peripheral blood progenitor cells as a graft, and 2.2 for patients who developed previous acute GVHD. MLC was not useful for predicting acute GVHD, but MLC with RR >4.5% associated with other risk factors could predict the development of chronic GVHD, being of help for the prevention and/or treatment of this late complication.

Effect of hydroxyurea on the intracellular multiplication of Toxoplasma gondii, Leishmania amazonensis and Trypanosoma cruzi

Toxoplasma gondii, Leishmania amazonensis and Trypanosoma cruzi are obligate intracellular parasites that multiply until lysis of host cells. The present study was undertaken to evaluate the effect of hydroxyurea (an inhibitor of cell division at the G1/S phase) on the multiplication of L. amazonensis, T. gondii, and T. cruzi in infected host cells. Infected cells were treated with hydroxyurea (4 mM) for 48 h. Hydroxyurea arrested intracellular multiplication of all infective forms of the parasites tested. In treated cultures, the percent of infected host cells decreased (50-97%) and most intracellular parasites were eliminated. Ultrastructural observations showed no morphologic change in host cells while intracellular parasites presented drastic morphologic alterations or disruption. The results strongly suggest that hydroxyurea was able to interfere with the multiplication of intracellular parasites, leading to an irreversible morphological effect on L. amazonensis, T. gondii, and T. cruzi without affecting the host cells.

Interaction between human cytomegalovirus UL136 protein and ATP1B1 protein

Interplay between the host and human cytomegalovirus (HCMV) has a pivotal role in the outcome of infection. A region (referred to as UL/b’) present in the Toledo strain of HCMV and low passage clinical isolates contains 19 additional genes, which are absent in the highly passaged laboratory strain AD169. Products of the UL/b’ genes may determine the manifestations of HCMV infection in vivo. However, little is known about the host factors, which interact with UL/b’ proteins. This study was conducted to investigate the function of the HCMV UL136 protein. By yeast two-hybrid screening, the β1 subunit of the host Na+/K+-ATPase (ATP1B1) was identified to be a candidate protein, which interacts with the HCMV UL136 protein. The interaction was further evaluated both in vitro by pull-down assay and in vivo by immunofluorescent co-localization. The results showed that the UL136 protein can interact with ATP1B1 in vitro. Co-localization of UL136-EGFP and ATP1B1-DsRed in cell membranes suggests that ATP1B1 was a partner of the UL136 protein. It can be proposed that the HCMV UL136 protein may have important roles in processes such as cell-to-cell spread, and in maintaining cell osmotic pressure and intracellular ion homeostasis during HCMV infection.