共查询到20条相似文献,搜索用时 10 毫秒
1.
Lara FA Sant'anna C Lemos D Laranja GA Coelho MG Reis Salles I Michel A Oliveira PL Cunha-E-Silva N Salmon D Paes MC 《Biochemical and biophysical research communications》2007,355(1):16-22
Epimastigotes multiplies in the insect midgut by taking up nutrients present in the blood meal including heme bound to hemoglobin of red blood cell. During blood meal digestion by vector proteases in the posterior midgut, hemoglobin is clipped off into amino acids, peptides, and free heme. In this paper, we compared the heme and hemoglobin uptake kinetics and followed their intracellular trafficking. Addition of heme to culture medium increased epimastigote proliferation in a dose-dependent manner, while medium supplemented with hemoglobin enhanced growth after 3-day lag phase. Medium supplemented with globin-derived peptides stimulated cell proliferation in a dose-independent way. Using Palladium mesoporphyrin IX (Pd-mP) as a fluorescent heme-analog, we observed that heme internalization proceeded much faster than that observed by hemoglobin-rhodamine. Binding experiments showed that parasites accumulated the Pd-mP into the posterior region of the cell whereas hemoglobin-rhodamine stained the anterior region. Finally, using different specific inhibitors of ABC transporters we conclude that a P-glycoprotein homologue transporter is probably involved in heme transport through the plasma membrane. 相似文献
2.
Alicia Vázquez Juan de Dios Ruiz-Rosado Luis I. Terrazas Imelda Juárez Lorena Gomez-Garcia Elsa Calleja Griselda Camacho Ana Chávez Miriam Romero Tonathiu Rodriguez Bertha Espinoza Miriam Rodriguez-Sosa 《International journal of biological sciences》2014,10(8):909-920
The C-type lectin receptor mMGL is expressed exclusively by myeloid antigen presenting cells (APC) such as dendritic cells (DC) and macrophages (Mφ), and it mediates binding to glycoproteins carrying terminal galactose and α- or β-N-acetylgalactosamine (Gal/GalNAc) residues. Trypanosoma cruzi (T. cruzi) expresses large amounts of mucin (TcMUC)-like glycoproteins. Here, we show by lectin-blot that galactose moieties are also expressed on the surface of T. cruzi. Male mMGL knockout (-/-) and wild-type (WT) C57BL/6 mice were infected intraperitoneally with 104
T. cruzi trypomastigotes (Queretaro strain). Following T. cruzi infection, mMGL-/- mice developed higher parasitemia and higher mortality rates compared with WT mice. Although hearts from T. cruzi-infected WT mice presented few amastigote nests, mMGL-/- mice displayed higher numbers of amastigote nests. Compared with WT, Mφ from mMGL-/- mice had low production of nitric oxide (NO), interleukin (IL)-12 and tumor necrosis factor (TNF)-α in response to soluble T. cruzi antigens (TcAg). Interestingly, upon in vitro T. cruzi infection, mMGL-/- Mφ expressed lower levels of MHC-II and TLR-4 and harbored higher numbers of parasites, even when mMGL-/- Mφ were previously primed with IFN-γ or LPS/IFN-γ. These data suggest that mMGL plays an important role during T. cruzi infection, is required for optimal Mφ activation, and may synergize with TLR-4-induced pathways to produce TNF-α, IL-1β and NO during the early phase of infection. 相似文献
3.
4.
Alvarez MN Piacenza L Irigoín F Peluffo G Radi R 《Archives of biochemistry and biophysics》2004,432(2):222-232
We studied the capacity of macrophage-derived peroxynitrite to diffuse into and exert cytotoxicity against Trypanosoma cruzi, the causative agent of Chagas' disease. In two types of macrophage-T. cruzi co-cultures, one with a fixed separation distance between source and target cells, and another involving cell-to-cell interactions, peroxynitrite resulted in significant oxidation of intracellular dihydrorhodamine and inhibition of [(3)H]thymidine incorporation in T. cruzi, which were not observed by superoxide or nitric oxide alone. The effects were attenuated in the presence of bicarbonate, in agreement with the extracellular consumption of peroxynitrite by its fast reaction with CO(2). However, studies using different T. cruzi densities, which allow to modify average diffusion distances of exogenously added peroxynitrite to target cells, indicate that at distances <5 microm, the diffusion process outcompetes the reaction with CO(2) and that the levels of peroxynitrite formed by macrophages would be sufficient to cause toxicity to T. cruzi during cell-to-cell contact and/or inside the phagosome. 相似文献
5.
Cathepsin D activity was estimated in midgut homogenates from Rhodnius prolixus, uninfected and experimentally infected with Trypanosoma cruzi, at different times after blood ingestion. No enzyme activity was found in the anterior midgut and rectum. In the posterior midgut, enzyme activity was found both in lumen and wall. In starved uninfected insects, in lumen and wall, cathepsin D activity was high, decreasing to a constant rate at 1-15 days after feeding. In insects infected with T. cruzi cathepsin D activity increased 1 and 3 days after blood meal. We suggest that these changes in cathepsin D activity in R. prolixus posterior midgut are due to the establishment of T. cruzi infection. 相似文献
6.
Metacaspases are distant relatives of animal caspases present in plants, fungi and protozoa. At variance with caspases, metacaspases exhibit stringent specificity for basic amino-acid residues and are absolutely dependent on millimolar concentrations of calcium. In the protozoan parasite Trypanosoma cruzi, metacaspases have been suggested to be involved in an apoptosis-like phenomenon upon exposure of the parasite to fresh human serum (FHS). Nuclear relocalization of metacaspases was observed after FHS treatment and overexpression of metacaspase-5 led to enhanced sensitivity to this stimulus. Here we report some biochemical properties of T. cruzi metacaspases. Performing fluorescent-activated cell sorting (FACS) analysis of epimastigotes inducibly overexpressing metacaspase-3, we demonstrate a role for this metacaspase in cell cycle progression, protection of epimastigotes from naturally occurring cell death and differentiation to infective metacyclic trypomastigotes. We also show that regulation of metacaspase-3 activity is important for cell cycle completion inside the mammalian host. On the other hand, inducible overexpression of metacaspase-5 lacking its C-terminal domain caused an apoptotic-like response. These results suggest that the two T. cruzi metacaspases could play an important role in the life cycle and bring to light the close relationship between cell division, death and differentiation in this ancient unicellular eukaryote. 相似文献
7.
Désio Aurélio Farias-de-Oliveira Vinícius Cotta-de-Almeida Déa Maria S. Villa-Verde Ingo Riederer Juliana de Meis Wilson Savino 《Memórias do Instituto Oswaldo Cruz》2013,108(7):825-831
Developing thymocytes interact with thymic epithelial cells (TECs) through cell-cell
interactions, TEC-derived secretory moieties and extracellular matrix (ECM)-mediated
interactions. These physiological interactions are crucial for normal thymocyte
differentiation, but can be disrupted in pathological situations. Indeed, there is severe
thymic atrophy in animals acutely infected with Trypanosoma cruzi due to
CD4+CD8+ thymocyte depletion secondary to caspase-mediated apoptosis, together with
changes in ECM deposition and thymocyte migration. We studied an in vitro model of TEC
infection by T. cruzi and found that infected TEC cultures show a reduced
number of cells, which was likely associated with decreased proliferative capacity, but
not with increased cell death, as demonstrated by bromodeoxyuridine and annexin-V
labelling. The infected TEC cultures exhibited increased expression of fibronectin (FN),
laminin (LM) and type IV collagen. Importantly, treatment with FN increased the relative
number of infected cells, whereas treatment with anti-FN or anti-LM antibodies resulted in
lower infection rates. Consistent with these data, we observed increased thymocyte
adhesion to infected TEC cultures. Overall, these results suggest that ECM molecules,
particularly FN, facilitate infection of the thymic epithelium and that the consequent
enhancement of ECM expression might be associated with changes in TEC-thymocyte
interactions. 相似文献
8.
Salmon D do Aido-Machado R Diehl A Leidert M Schmetzer O de A Lima AP Scharfstein J Oschkinat H Pires JR 《Journal of molecular biology》2006,357(5):1511-1521
A Trypanosoma cruzi cysteine protease inhibitor, termed chagasin, is the first characterized member of a new family of tight-binding cysteine protease inhibitors identified in several lower eukaryotes and prokaryotes but not present in mammals. In the protozoan parasite T.cruzi, chagasin plays a role in parasite differentiation and in mammalian host cell invasion, due to its ability to modulate the endogenous activity of cruzipain, a lysosomal-like cysteine protease. In the present work, we determined the solution structure of chagasin and studied its backbone dynamics by NMR techniques. Structured as a single immunoglobulin-like domain in solution, chagasin exerts its inhibitory activity on cruzipain through conserved residues placed in three loops in the same side of the structure. One of these three loops, L4, predicted to be of variable length among chagasin homologues, is flexible in solution as determined by measurements of (15)N relaxation. The biological implications of structural homology between chagasin and other members of the immunoglobulin super-family are discussed. 相似文献
9.
10.
Nívia Carolina Nogueira-Paiva Kátia da Silva Fonseca Paula Melo de Abreu Vieira Lívia Figueiredo Diniz Ivo Santana Caldas Sandra Aparecida Lima de Moura Vanja Maria Veloso Paulo Marcos da Matta Guedes Washington Luiz Tafuri Maria Terezinha Bahia Cláudia Martins Carneiro 《Memórias do Instituto Oswaldo Cruz》2014,109(1):51-60
Chagasic megaoesophagus and megacolon are characterised by motor abnormalities
related to enteric nervous system lesions and their development seems to be related
to geographic distribution of distinct Trypanosoma cruzi
subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T.
cruzi strains and necropsied during the acute or chronic phase of
experimental disease for post mortem histopathological evaluation of
the oesophagus and colon. Both strains infected the oesophagus and colon and caused
an inflammatory response during the acute phase. In the chronic phase, inflammatory
process was observed exclusively in the Be-78 infected animals, possibly due to a
parasitism persistent only in this group. Myenteric denervation occurred during the
acute phase of infection for both strains, but persisted chronically only in Be-78
infected animals. Glial cell involvement occurred earlier in animals infected with
the Y strain, while animals infected with the Be-78 strain showed reduced glial
fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic
phase. These results suggest that although both strains cause lesions in the
digestive tract, the Y strain is associated with early control of the lesion, while
the Be-78 strain results in progressive gut lesions in this model. 相似文献
11.
12.
Espinoza B Solorzano-Domínguez N Vizcaino-Castillo A Martínez I Elias-López AL Rodríguez-Martínez JA 《International journal of biological sciences》2011,7(9):1357-1370
Mexican Ninoa and Queretaro (Qro) TcI strains of Trypanosoma cruzi have shown different degrees of virulence, and the two strains produce heterogeneous immune responses in the hearts of infected mice. This work shows that the same strains can invade the intestine by an intraperitoneal route and establish an infection, mainly in the colon. The three segments of the small intestine (duodenum, jejunum and ileum) were infected to a lesser degree than the colon. Despite the fact that parasites were predominantly found in the colon, an obvious inflammatory reaction was observed in the submucosal layer along the entire intestinal tract, with the virulent Qro strain causing significantly more areas of higher immune infiltration. A clear recruitment of CD4+ and CD8+ T lymphocytes to the mesenteric ganglia was observed during infection with the virulent strain. Macrophages were also differentially distributed in the gastrointestinal tract. These later cells infiltrated fewer amastigote nests in the mice infected with the Qro strain than in the mice infected with the Ninoa strain. When IFN-γ, TNF-α, and IL-4 levels were measured, an increase in these cytokines was observed compared with the uninfected mice. The role of these inflammatory reactions in the pathogenesis of Chagas enteropathy is also discussed in this paper. 相似文献
13.
de Melo LD Nepomuceno-Silva JL Sant'Anna C Eisele N Ferraro RB Meyer-Fernandes JR de Souza W Cunha-e-Silva NL Lopes UG 《Biochemical and biophysical research communications》2004,323(3):1009-1016
Here we have investigated the function of TcRho1, a Rho family orthologue from the parasite Trypanosoma cruzi. We have selected parasites overexpressing wild-type TcRho1 and a truncated form of TcRho1 (TcRho1-DeltaCaaX) which is unable to undergo farnesylation and supposed to interfere with recruitment of Rho effectors to membranes. TcRho1 protein was localized at the anterior region of wild-type and TcRho1 overexpressing epimastigotes, suggesting association with the Golgi apparatus. Accordingly, parasites overexpressing TcRho1-DeltaCaaX presented cytoplasmic fluorescence. To address the function of TcRho1 during differentiation, from epimastigotes to trypomastigotes, we submitted parasites overexpressing the above-cited lineages to metacyclogenesis assays. Parasites overexpressing TcRho1-DeltaCaaX generated a discrete number of metacyclic trypomastigotes when compared with other lineages. Strikingly, TcRho1-DeltaCaaX cells died synchronously during the process of metacyclogenesis. 相似文献
14.
Yeo M Acosta N Llewellyn M Sánchez H Adamson S Miles GA López E González N Patterson JS Gaunt MW de Arias AR Miles MA 《International journal for parasitology》2005,35(2):225-233
Trypanosoma cruzi, the causative agent of Chagas disease, has at least two principal intraspecific subdivisions, T. cruzi I (TCI) and T. cruzi II (TCII), the latter containing up to five subgroups (a-e). Whilst it is known that TCI predominates from the Amazon basin northwards and TCII to the South, where the disease is considered to be clinically more severe, the precise clinical and evolutionary significance of these divisions remains enigmatic. Here, we present compelling evidence of an association between TCI and opossums (Didelphis), and TCII and armadillos, on the basis of key new findings from the Paraguayan Chaco region, together with a comprehensive analysis of historical data. We suggest that the distinct arboreal and terrestrial ecologies, respectively, of these mammal hosts provide a persuasive explanation for the extant T. cruzi intraspecific diversity in South America, and for separate origins of Chagas disease in northern South America and in the southern cone countries. 相似文献
15.
Michael Z. Levy Aaron Tustin Ricardo Castillo-Neyra Tarub S. Mabud Katelyn Levy Corentin M. Barbu Victor R. Quispe-Machaca Jenny Ancca-Juarez Katty Borrini-Mayori Cesar Naquira-Velarde Richard S. Ostfeld and the Chagas Disease Working Group in Arequipa 《Proceedings. Biological sciences / The Royal Society》2015,282(1810)
Faeces-mediated transmission of Trypanosoma cruzi (the aetiological agent of Chagas disease) by triatomine insects is extremely inefficient. Still, the parasite emerges frequently, and has infected millions of people and domestic animals. We synthesize here the results of field and laboratory studies of T. cruzi transmission conducted in and around Arequipa, Peru. We document the repeated occurrence of large colonies of triatomine bugs (more than 1000) with very high infection prevalence (more than 85%). By inoculating guinea pigs, an important reservoir of T. cruzi in Peru, and feeding triatomine bugs on them weekly, we demonstrate that, while most animals quickly control parasitaemia, a subset of animals remains highly infectious to vectors for many months. However, we argue that the presence of these persistently infectious hosts is insufficient to explain the observed prevalence of T. cruzi in vector colonies. We posit that seasonal rains, leading to a fluctuation in the price of guinea pig food (alfalfa), leading to annual guinea pig roasts, leading to a concentration of vectors on a small subpopulation of animals maintained for reproduction, can propel T. cruzi through vector colonies and create a considerable force of infection for a pathogen whose transmission might otherwise fizzle out. 相似文献
16.
Bustamante JM Rivarola HW Fernández AR Enders JE Fretes R Palma JA Paglini-Oliva PA 《International journal for parasitology》2002,32(7):889-896
In two murine models we studied Trypanosoma cruzi reinfection in the acute and chronic phase of experimental Chagas' disease in order to elucidate the relevance of reinfections in determining the variability of cardiac symptoms and the irreversible cardiac damage. They were followed for 120 and 600 days post infection (p.i.) for the acute and chronic model, respectively. Reinfected mice reached higher parasitaemia levels than infected mice. The survival was 33 and 21% in the chronic phase for mice reinfected in the acute phase and 13% for mice reinfected in the chronic stage at the end of the experiments. Sixty-six percent of the infected group presented electrocardiographic abnormalities (heart frequency, prolonged PQ segment or QRS complex) in the chronic stage whereas 100% of the reinfected animals exhibited electric cardiac dysfunction since 90 and 390 days p.i. for the acute and chronic reinfected model, respectively (P<0.01). Heart histopathological studies showed fibrosis and necrosis areas and mononuclear infiltrates supporting the view that parasite persistence is a major factor in continuing the tissue inflammation. This work shows that T. cruzi reinfections could be related to the variability and severity of the clinical course of Chagas' disease and that parasite persistence is involved in exacerbation of the disease. 相似文献
17.
Claudia Mendon?a Bezerra Luciano Pamplona de Góes Cavalcanti Rita de Cássia Moreira de Souza Silvia Ermelinda Barbosa Samanta Cristina das Chagas Xavier Ana Maria Jansen Relrison Dias Ramalho Liléia Diotaiut 《Memórias do Instituto Oswaldo Cruz》2014,109(7):887-898
The role played by different mammal species in the maintenance of Trypanosoma
cruzi is not constant and varies in time and place. This study aimed to
characterise the importance of domestic, wild and peridomestic hosts in the
transmission of T. cruzi in Tauá, state of Ceará, Caatinga area,
Brazil, with an emphasis on those environments colonised by Triatoma
brasiliensis. Direct parasitological examinations were performed on
insects and mammals, serologic tests were performed on household and outdoor mammals
and multiplex polymerase chain reaction was used on wild mammals. Cytochrome b was
used as a food source for wild insects. The serum prevalence in dogs was 38% (20/53),
while in pigs it was 6% (2/34). The percentages of the most abundantly infected wild
animals were as follows: Thrichomys laurentius 74% (83/112)
and Kerodon rupestris 10% (11/112). Of the 749 triatomines
collected in the household research, 49.3% (369/749) were positive for T.
brasiliensis, while 6.8% were infected with T. cruzi
(25/369). In captured animals, T. brasiliensis shares a
natural environment with T. laurentius, K.
rupestris, Didelphis albiventris, Monodelphis
domestica, Galea spixii, Wiedomys
pyrrhorhinos, Conepatus semistriatus and Mus
musculus. In animals identified via their food
source, T. brasiliensis shares a natural environment with
G. spixii, K. rupestris, Capra hircus, Gallus
gallus, Tropidurus oreadicus and Tupinambis merianae.
The high prevalence of T. cruzi in household and peridomiciliar
animals reinforces the narrow relationship between the enzootic cycle and humans in
environments with T. brasiliensis and characterises it as
ubiquitous. 相似文献
18.
Azael Salda?a José E Calzada Vanessa Pineda Milixa Perea Chystrie Rigg Kadir González Ana Maria Santamaria Nicole L Gottdenker Luis F Chaves 《Memórias do Instituto Oswaldo Cruz》2015,110(7):936-944
Chagas disease, caused by Trypanosoma cruzi infection, is a zoonosis
of humans, wild and domestic mammals, including dogs. In Panama, the main T.
cruzi vector is hodnius pallescens, a triatomine bug
whose main natural habitat is the royal palm, Attalea butyracea. In
this paper, we present results from three T. cruzi serological tests
(immunochromatographic dipstick, indirect immunofluorescence and ELISA) performed in
51 dogs from 24 houses in Trinidad de Las Minas, western Panama. We found that nine
dogs were seropositive (17.6% prevalence). Dogs were 1.6 times more likely to become
T. cruzi seropositive with each year of age and 11.6 times if
royal palms where present in the peridomiciliary area of the dog''s household or its
two nearest neighbours. Mouse-baited-adhesive traps were employed to evaluate 12
peridomestic royal palms. All palms were found infested with R.
pallescens with an average of 25.50 triatomines captured per palm. Of 35
adult bugs analysed, 88.6% showed protozoa flagellates in their intestinal contents.
In addition, dogs were five times more likely to be infected by the presence of an
additional domestic animal species in the dog''s peridomiciliary environment. Our
results suggest that interventions focused on royal palms might reduce the exposure
to T. cruzi infection. 相似文献
19.
Cordeiro AT Cáceres AJ Vertommen D Concepción JL Michels PA Versées W 《Journal of molecular biology》2007,372(5):1215-1226
Glucose is an essential substrate for Trypanosoma cruzi, the protozoan organism responsible for Chagas' disease. The glucose is intracellularly phosphorylated to glucose 6-phosphate. Previously, a hexokinase responsible for this phosphorylation has been characterized. Recently, we identified an ATP-dependent glucokinase in T. cruzi exhibiting a tenfold lower substrate affinity compared to the hexokinase. Both enzymes, which belong to very different groups of the same family, are located inside glycosomes, the peroxisome-like organelles of Kinetoplastida that are known to contain the first seven glycolytic steps as well as enzymes of the oxidative branch of the pentose phosphate pathway. Here, we present the crystallographic structure of T. cruzi glucokinase, in complex with glucose and ADP. The structure suggests a loose tetrameric assembly formed by the association of two tight dimers. TcGlcK was previously reported to exist in a concentration-dependent equilibrium of monomeric and dimeric states. Here, we used mass spectrometry analysis to confirm the existence of TcGlcK monomeric and dimeric states. The analysis of subunit interactions and comparison with the bacterial glucokinases give insights into the forces promoting the stability of the different oligomeric states. Each T. cruzi glucokinase monomer contains one glucose and one ADP molecule. In contrast to hexokinases, which show a moderate preference for the alpha anomer of glucose, the electron density clearly shows the d-glucose bound in the beta configuration in the T.cruzi glucokinase. Kinetic assays with alpha and beta-d-glucose further confirm a moderate preference of the T. cruzi glucokinase for the beta anomer. Structural comparison of the glucokinase and hexokinases permits the identification of a possible mechanism for anomer selectivity in these hexose-phosphorylating enzymes. The preference for distinct anomers suggests that in T. cruzi hexokinase and glucokinase are not directly competing for the same substrate and are probably both present because they exert distinct physiological functions. 相似文献
20.
Acidocalcisomes are dense, acidic organelles with a high concentration of phosphorus present as pyrophosphate and polyphosphate complexed with calcium and other cations. Acidocalcisomes have been linked to the contractile vacuole complex in Chlamydomonas reinhardtii, Dictyostelium discoideum, and Trypanosoma cruzi. A microtubule- and cyclic AMP-mediated fusion of acidocalcisomes to the contractile vacuole complex in T. cruzi results in translocation of aquaporin and the resulting water movement which, in addition to swelling of acidocalcisomes, is responsible for the volume reversal not accounted for by efflux of osmolytes. Polyphosphate hydrolysis occurs during hyposmotic stress, probably increasing the osmotic pressure of the contractile vacuole and facilitating water movement. 相似文献