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1.
Veloso VM Guedes PM Andrade IM Caldas IS Martins HR Carneiro CM Machado-Coelho GL de Lana M Galvão LM Bahia MT Chiari E 《Memórias do Instituto Oswaldo Cruz》2008,103(6):528-534
The goals of the present study were to evaluate the kinetics of blood parasitism by examination of fresh blood, blood culture (BC) and PCR assays and their correlation with heart parasitism during two years of infection in Beagle dogs inoculated with the Be-78, Y and ABC Trypanosoma cruzi strains. Our results showed that the parasite or its kDNA is easily detected during the acute phase in all infected animals. On the other hand, a reduced number of positive tests were verified during the chronic phase of the infection. The frequency of positive tests was correlated with T. cruzi strain. The percentage of positive BC and blood PCR performed in samples from animals inoculated with Be-78 and ABC strains were similar and significantly larger in relation to animals infected with the Y strain.Comparison of the positivity of PCR tests performed using blood and heart tissue samples obtained two years after infection showed two different patterns associated with the inoculated T. cruzi strain: (1) high PCR positivity for both blood and tissue was observed in animals infected with Be-78 or ABC strains; (2) lower and higher PCR positivity for the blood and tissue, respectively, was detected in animals infected with Y strains. These data suggest that the sensitivity of BC and blood PCR was T. cruzi strain dependent and, in contrast, the heart tissue PCR revealed higher sensitivity regardless of the parasite stock. 相似文献
2.
Ana Luiza Cassin Duz Paula Melo de Abreu Vieira Bruno Mendes Roatt Rodrigo Dian Oliveira Aguiar-Soares Jamille Mirelle de Oliveira Cardoso Flávia Carvalho Bitencourt de Oliveira Levi Eduardo Soares Reis Washington Luiz Tafuri Vanja Maria Veloso Alexandre Barbosa Reis Cláudia Martins Carneiro 《Memórias do Instituto Oswaldo Cruz》2014,109(8):1005-1013
Trypanosoma cruzi infection may be caused by different strains with
distinct discrete typing units (DTUs) that can result in variable clinical forms of
chronic Chagas disease. The present study evaluates the immune response and cardiac
lesions in dogs experimentally infected with different T. cruzi
strains with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI
and TcII DTU, respectively. During infection with the Col strain, increased levels of
alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were observed. In
addition, CD8+ T-lymphocytes isolated from the peripheral blood produced
higher levels of interleukin (IL)-4. The latter suggests that during the acute phase,
infection with the Col strain may remain unnoticed by circulating mononuclear cells.
In the chronic phase, a significant increase in the number of inflammatory cells was
detected in the right atrium. Conversely, infection with the Y strain led to
leucopoenia, thrombopoenia, inversion of the ratio of CD4+/CD8+
T-lymphocytes and alterations in monocyte number. The Y strain stimulated the
production of interferon-γ by CD4+ and CD8+ T-lymphocytes and
IL-4 by CD8+ T-cells. In the chronic phase, significant heart inflammation
and fibrosis were observed, demonstrating that strains of different DTUs interact
differently with the host. 相似文献
3.
Camila Fran?a Campos Silvia Dantas Cangussú Ana Luiza Cassin Duz Christiane Teixeira Cartelle Maria de Lourdes Noviello Vanja Maria Veloso Maria Terezinha Bahia Camila Megale Almeida-Leite Rosa Maria Esteves Arantes 《PloS one》2016,11(4)
We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11th day after infection, a sub-group was euthanized (acute-phase group) and another sub-group was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatory-induced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic megacolon in mice that mimics the human disease, which persists for several years and has not been fully elucidated. We hypothesize that the long-term inflammatory process mediates neuronal damage and intramuscular and intramural denervation, leading to phenotypic changes in smooth muscle cells associated with fibrosis. These long-term structural changes may represent the basic mechanism for the formation of the Chagasic megacolon. 相似文献
4.
Maria Terezinha Bahia Isabel Mayer de Andrade Tassiane Ass��ria Fontes Martins ��lvaro Fernando da Silva do Nascimento L��via de Figueiredo Diniz Ivo Santana Caldas Andr�� Talvani Bernadette Bourdin Trunz Els Torreele Isabela Ribeiro 《PLoS neglected tropical diseases》2012,6(11)
Background
New safe and effective treatments for Chagas disease (CD) are urgently needed. Current chemotherapy options for CD have significant limitations, including failure to uniformly achieve parasitological cure or prevent the chronic phase of CD, and safety and tolerability concerns. Fexinidazole, a 2-subsituted 5-nitroimidazole drug candidate rediscovered following extensive compound mining by the Drugs for Neglected Diseases initiative and currently in Phase I clinical study for the treatment of human African trypanosomiasis, was evaluated in experimental models of acute and chronic CD caused by different strains of Trypanosoma cruzi.Methods and Findings
We investigated the in vivo activity of fexinidazole against T. cruzi, using mice as hosts. The T. cruzi strains used in the study were previously characterized in murine models as susceptible (CL strain), partially resistant (Y strain), and resistant (Colombian and VL-10 strains) to the drugs currently in clinical use, benznidazole and nifurtimox. Our results demonstrated that fexinidazole was effective in suppressing parasitemia and preventing death in infected animals for all strains tested. In addition, assessment of definitive parasite clearance (cure) through parasitological, PCR, and serological methods showed cure rates of 80.0% against CL and Y strains, 88.9% against VL-10 strain, and 77.8% against Colombian strain among animals treated during acute phase, and 70% (VL-10 strain) in those treated in chronic phase. Benznidazole had a similar effect against susceptible and partially resistant T. cruzi strains. Fexinidazole treatment was also shown to reduce myocarditis in all animals infected with VL-10 or Colombian resistant T. cruzi strains, although parasite eradication was not achieved in all treated animals at the tested doses.Conclusions
Fexinidazole is an effective oral treatment of acute and chronic experimental CD caused by benznidazole-susceptible, partially resistant, and resistant T. cruzi. These findings illustrate the potential of fexinidazole as a drug candidate for the treatment of human CD. 相似文献5.
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
6.
This paper describes the development of experimental Chagas' disease in 64 out-bred young dogs. Twenty-nine animals were inoculated with the Be-62 and 35 with Be-78 Trypanosoma cruzi strains. Twenty-six were infected with blood trypomastigotes by different inoculation routes and 38 with metacyclic trypomastigotes from the vector via the conjunctival route. Twenty of the 26 dogs infected with blood trypomastigotes were autopsied during the acute phase. Eleven died spontaneously and nine were sacrificed. Six remained alive until they died suddenly (two) or were autopsied. (four). Twelve of the 38 dogs infected with metacyclic trypomastigotes evolved naturally to the chronic phase and remained alive for 24-48 months. The parasitemia, clinical aspects and serology (IgM and IgG) as well as electrocardiogram, hemogram and heart anatomo-histopathologic patterns of acute and chronic cardiac forms of Chagas' disease as seen in human infections, were reproduced. The most important finding is the reproducibility of diffuse fibrosing chronic chagasic cardiopathy in all dogs infected with Be-78 T. cruzi strain autopsied between the 90th and 864th days of infection. Thus, the dog can be considered as a suitable experimental model to study Chagas' disease according to the requisites of the Word Health Organization (1984). Furthermore the animal is easily obtained and easy to handle and maintain in experimental laboratory conditions. 相似文献
7.
Guerra-Lopes ES Caldeira JC Santos CD Toldo MP Faccioli LH Sá-Nunes A Albuquerque S Prado JC 《Experimental parasitology》2008,120(1):10-14
Glucocorticoid hormones have been implicated as an important modulator of Trypanosoma cruzi pathogenesis. Since adrenal steroid hormones play a fundamental role in modulating the immune response, we hypothesized that adrenalectomy affect the course of the experimental T. cruzi infection. This study was undertaken to determine the effects of adrenalectomy during the acute phase of T. cruzi infection. Blood and tissue parasitism, macrophages, nitric oxide (NO) production and IFN-γ were evaluated in male Wistar rats infected with the Y strain of T. cruzi. Our results show that adrenalectomized rats displayed increased number of blood and heart parasites accompanied by decreases in the total number of peritoneal macrophages and IFN-γ when compared to controls. Adrenalectomy also reduced the levels of NO released from peritoneal macrophages of infected animals. These results suggest that adrenal corticosteroid insufficiency due to adrenalectomy could be considered an important factor during development of acute phases of experimental Chagas’ disease, enhancing pathogenesis through disturbance of the host’s immune system. 相似文献
8.
Jaquelline Carla Valamiel de Oliveira-Silva Girley Francisco Machado-de-Assis Maykon Tavares Oliveira Nívia Carolina Noguieira Paiva Márcio Sobreira Silva Araújo Cláudia Martins Carneiro Olindo Assis Martins-Filho Helen Rodrigues Martins Marta de Lana 《Memórias do Instituto Oswaldo Cruz》2015,110(1):86-94
Trypanosoma cruzi strains from distinct geographic areas show differences in drug
resistance and association between parasites genetic and treatment response has been
observed. Considering that benznidazole (BZ) can reduce the parasite burden and
tissues damage, even in not cured animals and individuals, the goal is to assess the
drug response to BZ of T. cruzi II strains isolated from children of the
Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected
and treated with BZ in both phases of infection were compared with the untreated and
evaluated by fresh blood examination, haemoculture, polymerase chain reaction,
conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in
the acute phase, a significant decrease in parasitaemia was observed for all strains.
Positive parasitological and/or serological tests in animals treated during the acute
and chronic (95.1-100%) phases showed that most of the strains were BZ resistant.
However, beneficial effect was demonstrated because significant reduction (p <
0.05%) and/or suppression of parasitaemia was observed in mice infected with all
strains (acute phase), associated to reduction/elimination of inflammation and
fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals,
what suggest that BZ use may be recommended at least for recent chronic infection of
the studied region. 相似文献
9.
Marcos Lazaro da Silva Guerreiro Isa Rita Brito Morais Sonia Gumes Andrade 《Memórias do Instituto Oswaldo Cruz》2015,110(4):500-506
Re-infections with Trypanosoma cruzi are an aggravating factor for
Chagas disease morbidity. The Colombian strain of T. cruzi
represents multiclonal populations formed by clonally propagating organisms with
different tropisms and degrees of virulence. In the present study, the influence of
successive inoculations with clones of the Colombian strain, exhibiting different
degrees of virulence, on chronic myocarditis and the humoral and cellular immune
responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence)
were demonstrated. Mice from three groups with a single infection were evaluated
during the acute (14th-30th day) and chronic phases for 175 days. An
immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous
test were also performed. Mice with a triple infection were studied on the
115th-175th days following first inoculation. The levels of IgM and IgG2a were higher
in the animals with a triple infection. DTH showed a higher intensity in the
inflammatory infiltrate based on the morphometric analysis during a 48 h period of
the triple infection and at 24 h with a single infection. The histopathology of the
heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed
by the morphometric test. The humoral responses indicate a reaction to the triple
infection, even with clones of the same strain. 相似文献
10.
J.R.P.T. Castanheira R.E.P. Castanho H. Rocha C. Pagliari M.I.S. Duarte A.L.S. Therezo E.F.B. Chagas L.P.A. Martins 《Parasitology international》2018,67(5):547-555
Trypanosoma cruzi infection stimulates inflammatory mediators which cause oxidative stress, and the use of antioxidants can minimize the sequelae of Chagas disease. In order to evaluate the efficacy of vitamin C in minimizing oxidative damage in Chagas disease, we orally administered ascorbic acid to Swiss mice infected with 5.0?×?104 trypomastigote forms of T. cruzi QM2 strain. These animals were treated for 60?days to investigate the acute phase and 180?days for the chronic phase. During the acute phase, the animals in the infected and treated groups demonstrated lower parasitemia and inflammatory processes were seen in more mice in these groups, probably due to the higher concentration of nitric oxide, which led to the formation of peroxynitrite. The decrease in reduced glutathione concentration in this group showed a circulating oxidant state, and this antioxidant was used to regenerate vitamin C. During the chronic phase, the animals in the infected and treated group showed a decrease in ferric reducing ability of plasma and uric acid concentrations as well as mobilization of bilirubin (which had higher plasma concentration), demonstrating cooperation between endogenous non-enzymatic antioxidants to combat increased oxidative stress. However, lower ferrous oxidation in xylenol orange concentrations was found in the infected and treated group, suggesting that vitamin C provided biological protection by clearing the peroxynitrite, attenuating the chronic inflammatory process in the tissues and favoring greater survival in these animals. Complex interactions were observed between the antioxidant systems of the host and parasite, with paradoxical actions of vitamin C. 相似文献
11.
Torriceli Souza Thé Renata Siqueira Portella Marcos Lázaro Guerreiro Sonia Gumes Andrade 《Memórias do Instituto Oswaldo Cruz》2013,108(6):691-698
Acute infection with Trypanosoma cruzi results in intense
myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The
evolution toward this chronic cardiac form occurs in approximately 30% of all
cases of T. cruzi infection. Suppression of delayed type
hypersensitivity (DTH) has been proposed as a potential explanation of the
indeterminate form. We investigated the effect of cyclophosphamide (CYCL)
treatment on the regulatory mechanism of DTH and the participation of heart
interstitial dendritic cells (IDCs) in this process using BALB/c mice
chronically infected with T. cruzi. One group was treated with
CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by
intradermal injection of T. cruzi antigen (3 mg/mL) in the
hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin
test revealed increased thickness in antigen-injected footpads, which was more
evident in the mice treated with CYCL than in those mice that did not receive
treatment. The thickened regions were characterised by perivascular infiltrates
and areas of necrosis. Intense lesions of the myocardium were present in
three/16 cases and included large areas of necrosis. Morphometric evaluation of
lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled
with specific antibodies (CD11b and CD11c) and T. cruzi
antigens were detected using a specific anti-T. cruzi antibody.
Identification of T. cruzi antigens, sequestered in these cells
using specific anti-T. cruzi antibodies was done, showing a
significant increase in the number of these cells in treated mice. These results
indicate that IDCs participate in the regulatory mechanisms of DTH response to
T. cruzi infection. 相似文献
12.
ANTONIANA URSINE KRETTLI 《The Journal of eukaryotic microbiology》1977,24(4):514-518
SYNOPSIS. The effect of malaria on the chronic phase of Chagas’disease was investigated in mice. The animals were given Plasmodium berghei-infected red blood cells 2 to 12 months after their initial inoculation with trypomastigotes of 3 different strains of Trypanosoma cruzi (Y, CL and Gilmar). In all the experiments carried out with one of the strains (CL), a somewhat variable but always considerable percentage of mice (average 39%) relapsed in to the acute phase of Chagas’disease. This relapse was characterized by a significant increase in the number of circulating trypomastigotes. Recrudescence was observed also with a 2nd strain of T. cruzi (Gilmar), which is similar in many aspects to the CL strain, e.g. the morphology of blood stages, curve of parasitemia and susceptibility to antibodies in vitro. In mice whose chronic phase was induced by trypomastigotes of the Y strain, malaria infections did not induce a typical acute phase with high parasitemia by T. cruzi. Bloodstream forms of Y parasites differ from those of CL and Gilmar strains morphologically as well as immunologically, i.e. only the Y strain is easily agglutinated and partly inactivated by specific immune serum. In light of this and other known characteristics of the strains used in the present work, the author speculates on mechanisms which allow malaria infections selectively to suppress acquired host resistance to certain strains of T. cruzi. 相似文献
13.
Daniel B. Liarte Silvane M.F. Murta Alvaro J. Romanha 《Experimental parasitology》2009,123(4):283-291
A multiplex PCR was developed for simultaneous detection of Trypanosoma cruzi DNA and classification of the parasite strain into groups I and II. As little as 10 fg of T. cruzi DNA could be detected by multiplex PCR. The technique was shown to be specific for T. cruzi DNA, since no PCR amplification products were obtained with DNA from other tripanosomatid species. Multiplex PCR was validated by assaying genomic DNA from 34 strains of T. cruzi that had been previously characterized; 24 blood samples from experimentally-infected mice and non-infected controls; 20 buffy coat samples from patients in the acute phase of Chagas disease and non-infected individuals, and 15 samples of feces from naturally-infected Triatoma infestans. T. cruzi samples from patients and from Y strain-infected mice were classified by multiplex PCR as T. cruzi II and samples from T. infestans and Colombiana strain-infected mice as T. cruzi I. 相似文献
14.
Christopher Steven Eickhoff Brian Anthony Dunn Nicole Lea Sullivan Daniel Fredric Hoft 《Memórias do Instituto Oswaldo Cruz》2013,108(4):508-511
Trypanosoma cruzi infects humans when infected triatomine
vector excreta contaminate breaks in skin or mucosal surfaces. T.
cruzi insect-derived metacyclic trypomastigotes (IMT) invade
through gastric mucosa after oral challenges without any visible inflammatory
changes, while cutaneous and conjunctival infections result in obvious local
physical signs. In this study we compared the infectivity of T.
cruzi IMT in mice after cutaneous and oral contaminative challenges
simulating natural infections. The 50% infective dose (ID50) for oral challenge
was 100 fold lower than the ID50for cutaneous challenge, indicating that oral
mucosal transmission is more efficient than cutaneous transmission. 相似文献
15.
Sabrina Cencig Nicolas Coltel Carine Truyens Yves Carlier 《PLoS neglected tropical diseases》2013,7(6)
This work aims to compare the effects of acute or chronic infections with the T. cruzi genotypes TcI (X10 strain), TcII (Y strain) and TcVI (Tulahuen strain) on fertility, gestation, pup growth and the possible vertical transmission of parasites in BALB/c mice. The occurrence of congenital infection was evaluated by microscopic examination of blood and/or qPCR on blood and heart in newborn pups and/or older offspring submitted to cyclophosphamide-induced immunosuppression in order to detect possible cryptic congenital infection. Altogether, the results show that: i) for the three strains tested, acute infection occurring after the embryo implantation in the uterus (parasite inoculation 4 days before mating), or close to delivery (parasite inoculation on day 13 of gestation), prevents or severely jeopardizes gestation outcome (inducing pup mortality and intra-uterine growth retardation); ii) for the three strains tested, gestation during chronic infection results in intra-uterine growth retardation, whereas re-inoculation of TcVI parasites during gestation in such chronically infected mice, in addition, strongly increases pup mortality; iii) congenital infection remains a rare consequence of infection (occurring in approximately 4% of living pups born to acutely infected dams); iv) PCR, detecting parasitic DNA and not living parasites, is not convenient to detect congenial infection close to delivery; v) transmission of parasites by breast milk is unlikely. This study should encourage further investigations using other parasite strains and genotypes to explore the role of virulence and other factors, as well as the mechanisms of such effects on gestation and on the establishment of congenital infection. 相似文献
16.
Coura-Vital W Carneiro CM Martins HR de Lana M Veloso VM Teixeira-Carvalho A Bahia MT Corrêa-Oliveira R Martins-Filho OA Tafuri WL Reis AB 《Experimental parasitology》2008,120(3):269-274
A detailed investigation has been carried out about the serological profiles of groups of dogs experimentally infected with metacyclic (MT) or blood (BT) trypomastigotes of Berenice-78 Trypanosoma cruzi strain. Peripheral blood was collected from infected dogs and uninfected controls, weekly during 35 days following the acute phase of infection, and immunoglobulin profiles were determined by ELISA. Dogs infected with BT exhibited unaltered levels of IgG2, increases in IgM, IgE, IgA, IgG and IgG1. In contrast, dogs infected with MT presented unaltered levels of IgE and IgG1 and an increase in IgM, IgA, IgG and IgG2 levels. Compared with the MT group, animals infected with BT showed significant increases in IgM on days 7, 14 and 28, in IgA on days 7, 14 and 21, in IgE on days 7 and 14, in IgG on days 14 and 28, and in IgG1 on days 7, 14 and 21. Parasitemia levels of the infected animals were measured over the same time period. No correlations were found between the immunoglobulin profiles and the parasitemia levels. The results demonstrated that the inoculum source (BT or MT) influence the immunoglobulin isotype profile that may drive distinct outcome of acute canine Chagas disease. 相似文献
17.
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
18.
Gisele Macêdo Rodrigues da Cunha Maíra Araújo Azevedo Denise Silva Nogueira Marianna de Carvalho Clímaco Edward Valencia Ayala Juan Atilio Jimenez Chunga Raul Jesus Ynocente La Valle Lucia Maria da Cunha Galvo Egler Chiari Carlos Ramon Nascimento Brito Rodrigo Pedro Soares Paula Monalisa Nogueira Ricardo Toshio Fujiwara Ricardo Gazzinelli Robert Hincapie Carlos-Sanhueza Chaves Fabricio Marcus Silva Oliveira M. G. Finn Alexandre Ferreira Marques 《PLoS neglected tropical diseases》2021,15(7)
Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T. cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue. 相似文献
19.
Federico Penas Gerardo A. Mirkin Eugenia Hovsepian Ágata Cevey Roberto Caccuri María Elena Sales Nora B. Goren 《生物化学与生物物理学报:疾病的分子基础》2013,1832(1):239-248
Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas' disease, causes cardiac alterations in the host. Although the main clinical manifestations arise during the chronic stage, the mechanisms leading to heart damage develop early during infection. In fact, an intense inflammatory response is observed from acute stage of infection. Recently, peroxisome proliferator-activated receptors (PPARs) have attracted research interest due to their participation in the modulation of inflammation. In this work we addressed the role of 15-Deoxy-?12,14 ProstaglandinJ2 (15dPGJ2), a PPARγ natural ligand in the regulation of inflammatory mediators, in acute and chronic experimental mouse models of Chagas' disease with the RA and K98 T. cruzi strains, respectively. This work demonstrates that 15dPGJ2 treatment inhibits the expression and activity of inducible nitric oxide synthase (NOS2) as well as TNF-α and IL-6 mRNA levels. Also, expression and activity of metalloproteinases 2 (MMP-2) and 9 (MMP9) were inhibited by 15dPGJ2. Moreover GW9662, a specific PPARγ antagonist, revealed the participation of other signaling pathways since, in GW9662 presence, 15dPJG2 had a partial effect on the inhibition of inflammatory parameters in the acute model of infection. Accordingly, NF-κB activation was demonstrated, assessing p65 nuclear translocation in the hearts of infected mice with both T. cruzi strains. Such effect was inhibited after 15dPGJ2 treatment. Our findings support the concept that in vivo PPARγ and NF-κB pathways are implicated in the inhibitory effects of 15dPGJ2 on inflammatory mediators at different times depending on whether the infection is caused by the lethal or non-lethal T. cruzi strain. 相似文献
20.
S.C. Bourguignon H.C. Castro C.R. Alves I.L. Gama W.S. Seguins 《Experimental parasitology》2009,122(2):91-96
Chagas disease is an endemic parasitic infection caused by Trypanosomacruzi that affects 18-20 million people in Central and South America. Recently we described the Epoxy-α-Lap, an oxyran derivative of α-lapachone, which presents a low toxicity profile and a high inhibitory activity against T.cruzi epimastigotes forms, the non-infective form of this parasite. In this work we described the trypanocidal effects of Epoxy-α-Lap on extracellular (trypomastigote) and intracellular (amastigote) infective forms of two T. cruzi strains (Y and Colombian) known by their different infective profile. Our results showed that Epoxy-α-Lap is lethal to trypomastigote Y and Colombian strains (97% and 84%, respectively). Interestingly, Epoxy-α-Lap also showed a trypanocidal effect in human macrophage infected with T. cruzi Y (85.6%) and Colombian (71.9%) strains amastigote forms. Similar effects were observed on T. cruzi amastigote infected Vero cells (96.4% and 95.0%, respectively). Our results pointed Epoxy-α-Lap as a potential candidate for Chagas disease chemotherapy since it presents trypanocidal activity on all T. cruzi forms with low) toxicity profile. 相似文献