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1.
The intracellular parasite Toxoplasma gondii can influence host resistance by modulating immune functions in various cell types. The stimulation of interleukin (IL)-12 production in macrophages, dendritic cells and neutrophils by T. gondii has been implicated to be important for skewing anti-parasite immunity early after infection as well as in mediating the pathologic effects induced by the parasite. The present study demonstrates secretion of IL-12 p40 and the bioactive p70 heterodimer by inflammatory macrophages following exposure to live Toxoplasma or tachyzoite lysate. Parasite induction of IL-12 occurred in a dose-dependent manner. Predigestion of T. gondii lysate with proteinase K abrogated its IL-12 inducing activity, thus indicating that a parasite protein(s) triggers this response. Macrophages from various mouse inbred strains showed a differential responsiveness: cells from T. gondii-susceptible mice released more IL-12 upon toxoplasmic challenge than those from resistant mice, although the infection rate and intracellular parasite growth were similar. In triggering macrophage production of IL-12, tachyzoites proved superior to bradyzoites prepared from the same T. gondii isolate. Furthermore, parasites of a mouse-virulent isolate became less efficient inducers of IL-12 following attenuation. The parallel loss in macrophage stimulation in vitro and acute virulence in vivo suggests a linkage of both parasite capacities. Together with the correlation on host side between the genotype-dependent mouse susceptibility to infection and cellular responsiveness to the parasite trigger, these findings indicate that an overproduction of parasite-induced IL-12 might represent a basic mechanism of T. gondii pathogenicity. 相似文献
2.
Schuindt SH Oliveira BC Pimentel PM Resende TL Retamal CA DaMatta RA Seipel D Arnholdt AC 《Veterinary parasitology》2012,186(3-4):207-215
Toxoplasmosis is a world wide spread zoonosis caused by Toxoplasma gondii, an obligate intracellular parasite that is able to disseminate into deep tissues and cross biological barriers, reaching immunoprivileged sites such as the brain and retina. The parasite is able to infect macrophages and dendritic cells for dispersal throughout the body. However, the molecular mechanisms or outcomes of the subversion of the host cell are largely unknown. Recently our group established that metalloproteinases are involved in migration of infected macrophages. Herein, we evaluated the recruitment of host invasive machinery components in T. gondii infected murine macrophages. We showed by immunoprecipitation assays that MMP-9, CD44 TIMP-1 and uPAR were secreted as a multi-protein complex by infected macrophages. Zymographic analysis revealed that MMP-9 was present in its pro- and active form. Moreover, inhibition of uPA/uPAR pathway by PAI-1 decreased secretion of MMP-9 active forms, as well those associated to uPAR and TIMP-1, but not to CD44. Data presented here suggest that MMP-9 is secreted as a multiprotein complex by T. gondii infected macrophages, similar to that observed in metastatic cells. We further speculate that uPA/uPAR system is involved in the expression/secretion of complexes containing active MMP-9 forms. 相似文献
3.
Toxoplasma gondii (T. gondii) invasion of host cells is a complicated process of interaction between parasites and host cells. In the present study we investigated the alterations of free Ca(2+) concentration ([Ca(2+)](i)) and cytoskeletons in phagocytic and non-phagocytic host cells and arachidonic acid (AA) concentration in cells supernatant during T. gondii invasion. T. gondii invasion induced significant elevation of intracellular [Ca(2+)](i) in phagocytic cells (J774A.1) but not in non-phagocytic cells (L929). Pre-treatment of J774A.1 cells with Phospholipase C (PLC) inhibitor (U73122), or Ca(2+) chelators (EGTA, BAPTA/AM) did not block elevations of [Ca(2+)](i) but the elevations were lower and of shorter duration than that in untreated cells. Pre-treatment of tachyzoites with Phospholipases A (PLA) inhibitors (4-BPB and AACOCF3) resulted in a similar pattern of increasing of [Ca(2+)](i) as that in Ca(2+) chelators treated cells. Agglutinations of microfilaments were observed in J774A.1 cells but not in L929 cells. No changes of microtubules were observed in either cell. Treatment of cells with cytoskeleton inhibitors (colchicines, cytochalasin-D) resulted in reduced cell infection ratios. AA concentration in J774A.1 cells supernatant reached 8.44-fold of basal concentration after T. gondii infection and those in 4-BPB or AACOCF3 pre-treated cells reached 7.70-fold and 8.09-fold of basal concentration, respectively. However, elevation of AA concentrations induced by 4-BPB or AACOCF3 treated tachyzoites were 3.02-fold and 2.65-fold of basal AA concentration. AA concentration in L929 cells supernatant reached 5.02-fold of basal concentration after T. gondii infection and those in 4-BPB or AACOCF3 pre-treated cells reached 4.75-fold and 4.78-fold of basal concentration, respectively. However, elevation of AA concentrations induced by 4-BPB or AACOCF3 treated tachyzoites were 2.06-fold and 2.43-fold of basal AA concentration. Results indicated that elevations of [Ca(2+)](i) and AA induced by T. gondii invasion were from both host cells and parasites. T. gondii invasion activated host cell PLC and triggered the PLC-PKC signal pathway, which resulted in the flowing of extracellular Ca(2+) and the releasing of intracellular Ca(2+) pool. Elevated [Ca(2+)](i) induced reorganization of host cell microfilaments. The invasion also activated secretory PLA(2) (sPLA(2)) and cytosolic PLA(2) (cPLA(2)) of the parasite to release AA, which increased the permeability of cell membrane. 相似文献
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5.
da Silva AV de Moraes Gimenes Bosco S Langoni H Bagagli E 《Veterinary parasitology》2006,135(1):81-83
Toxoplasmosis is a worldwide distributed zoonosis that affects man and most warm-blooded animals, with a great economic impact in animal and public health. Serum samples from nine 9-banded armadillos, three 6-banded armadillos, three coatimundis, two opossums and one nutria were submitted for anti-Toxoplasma gondii antibody detection by means of a modified direct agglutination method. Encephalic tissue of three 6-banded armadillos, one 9-banded armadillo, one coatimundi and one nutria were digested in acid pepsin solution and inoculated into Swiss mice for parasite isolation. Only one serum sample from a nine-banded armadillo and two from six-banded armadillos reacted producing titers equal to 256, 512 and 512, respectively. T. gondii was isolated in two 6-banded armadillos, one of which was not positive in the serological test. 相似文献
6.
Biology and epidemiology of Toxoplasma gondii in man and animals 总被引：6，自引：0，他引：6
Hill DE Chirukandoth S Dubey JP 《Animal health research reviews / Conference of Research Workers in Animal Diseases》2005,6(1):41-61
Toxoplasma gondii is a coccidian parasite which utilizes felids as definitive hosts, and which has an unusually wide intermediate host range. The parasite was initially described by Nicolle and Manceaux in 1908 from the rodent, Ctenodactylus gundi. Infection with T. gondii is one of the most common parasitic infections of man and other warm-blooded animals. It has been found worldwide from Alaska to Australia. Nearly one-third of humanity has been exposed to this parasite; serologic surveys indicate that T. gondii infections are common in wild carnivores, including pigs, bears, felids, fox, raccoons, and skunks. Clinical and subclinical toxoplasmosis has been reported from wild cervids, ungulates, marsupials, monkeys, and marine mammals. Southern sea otter populations have been severely impacted by Toxoplasma infections. 相似文献
7.
Portes Jde A Netto CD da Silva AJ Costa PR DaMatta RA dos Santos TA De Souza W Seabra SH 《Veterinary parasitology》2012,186(3-4):261-269
Toxoplasma gondii, the agent of Toxoplasmosis, is an obligate intracellular protozoan able to infect a wide range of vertebrate cells, including nonprofessional and professional phagocytes. Therefore, drugs must have intracellular activities in order to control this parasite. The most common therapy for Toxoplasmosis is the combination of sulfadiazine and pyrimethamine. This treatment is associated with adverse reactions, thus, the development of new drugs is necessary. In previous studies, naphthoquinone derivatives showed anti-cancer activity functioning as agents capable of acting on groups of DNA, preventing cancer cells duplication. These derivatives also display anti-parasitic activity against Plasmodium falciparum and Leishmania amazonensis. The derivative pterocarpanquinone tested in this work resulted from the molecular hybridization between pterocarpans and naphtoquinone that presents anti-tumoral and anti-parasitic activities of lapachol. The aim of this work was to determine if this derivative is able to change T. gondii growth within LLC-MK2 cells. The drug did not arrest host cell growth, but was able to decrease the infection index of T. gondii with an IC(50) of 2.5 μM. Scanning and transmission electron microscopy analysis showed morphological changes of parasites including membrane damage. The parasite that survived tended to encyst as seen by Dolichos biflorus lectin staining and Bag-1 expression. These results suggest that pterocarpanquinones are drugs potentially important for the killing and encystment of T. gondii. 相似文献
8.
Anti-protozoal efficacy of medicinal herb extracts against Toxoplasma gondii and Neospora caninum 总被引：1，自引：0，他引：1
The purpose of this study was to determine whether alcohol extracts of herbs (Sophora flavescens Aiton, Sinomenium acutum (Thunb.) Rehder and E.H. Wilson, Pulsatilla koreana (Yabe ex Nakai) Nakai ex T. Mori, Ulmus macrocarpa Hance and Torilis japonica (Houtt.) DC.) from South Korea, possess in vitro anti-protozoal activity against cultures of Toxoplasma gondii and Neospora caninum. These herbs have been used as human anti-parasitics in Asian countries for many years. Alcohol extracts of these herbs were serially diluted to final concentrations ranging from 625 to 19.5 ng/ml in media and added to wells containing either T. gondii or N. caninum tachyzoites in equine dermal (ED) cells. Parasite growth inhibition was measured using 3H-uracil incorporation as compared to untreated controls. T. japonica inhibited T. gondii proliferation by 99.3, 95.5, 73.0 and 54.0% in the range from 156 to 19.5 ng/ml, and S. flavescens inhibited T. gondii proliferation by 98.7, 83.0 and 27.2% in the range from 156 to 39 ng/ml. T. japonica inhibited N. caninum proliferation by 97.8, 97.9, 85.3 and 46.4% in the range from 156 to 19.5 ng/ml. S. flavescens inhibited N. caninum proliferation by 98.6, 97.0, 69.5 and 14.0% in the range from 156 to 19.5 ng/ml. Toxicity to host cells was noted when concentrations of T. japonica and S. flavescens exceeded 625 ng/ml. The herb extracts from S. acutum, Pulsatilla koreana, and U. macrocarpa also showed toxicity at higher levels but did not achieve the same inhibition effects at the lower concentrations against T. gondii and N. caninum as T. japonica and S. flavescens. 相似文献
9.
Anfray P Bonetti C Fabbrini F Magnino S Mancianti F Abramo F 《Veterinary dermatology》2005,16(2):131-136
A 9-year-old female, domestic short hair cat was presented with sudden onset of polyuria/polydipsia, and hundreds of cutaneous nodules. Prior to referral, the cat had had four skin nodules that were treated with steroids. The four skin nodules then multiplied to form more than 100 ulcerated and nonulcerated nodules located all over the trunk. Clinical evaluation revealed hypothermia and respiratory distress. Cytology from both skin nodules and bronchoalveolar lavage showed macrophages and small organisms whose shape and size were indicative of Toxoplasma spp., or similar organisms. Feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) serology results were negative. The cat was seropositive for Toxoplasma (IgG 1 : 640) and Neospora (1 : 80) infections. The cat died soon after referral. Necropsy revealed pyothorax, necrotic/purulent pneumonia, haemorrhagic spots on kidneys and mesentery. Histopathology from skin nodules showed diffuse, deep necrotic dermatitis/panniculitis, vasculitis and disseminated free and grouped protozoa. The parasites were found in lungs, spleen, kidneys and liver. Immunohistochemistry on skin tissue with anti-Toxoplasma gondii and Neospora caninum antibodies gave positive results with both. Electron microscopy showed single and grouped tachyzoites with morphological features of T. gondii, often within macrophages. Samples of cutaneous nodules and bronchoalveolar fluid were examined by a polymerase chain reaction (PCR) assay for detecting apicomplexa coccidia. PCR results were consistent only with T. gondii infection. Therefore, immunohistochemistry positivity for N. caninum was considered a cross-reaction and a diagnosis of cutaneous and visceral toxoplasmosis was made. 相似文献
10.
Martins-Duarte ES Lemgruber L Lorente SO Gros L Magaraci F Gilbert IH de Souza W Vommaro RC 《Veterinary parasitology》2011,177(1-2):157-161
Previous studies from our group have demonstrated the high susceptibility of Toxoplasma gondii tachyzoites to the sterol analogues 22,26-azasterol and 24,25-(R,S)-epiminolanosterol. In this work we present data on testing in vitro three novel azasterols as potential agents for the treatment of toxoplasmosis. The three compounds inhibited parasite growth at micromolar concentrations, in a dose-dependent manner. Electron microscopy analysis of intracellular tachyzoites after treatment with the most effective compound showed drastic mitochondrion swelling associated with the appearance of an electron-lucent matrix and disrupted cristae. Parasite lysis also took place. The appearance of electron dense cytoplasmic structures similar to amylopectin granules distributed throughout the parasite suggests that azasterols might be inducing differentiation of those tachyzoites which were not lysed to the bradyzoite stage. 相似文献
11.
I Esteban-Redondo S W Maley K Thomson S Nicoll S Wright D Buxton E A Innes 《Veterinary parasitology》1999,86(3):155-171
It has been reported in the literature that cattle are more resistant to toxoplasmosis than sheep. Congenital disease due to T. gondii infection is rarely reported in cattle whereas the parasite is a major cause of abortion and neonatal mortality in sheep. It is believed that sheep remain chronically infected for life. Undercooked meat from infected sheep is an important source of infection for man. In contrast cattle are thought to harbour fewer parasite tissue cysts which may not persist for the lifetime of the host. Therefore, cattle are believed to pose less of a risk for human infection. In this study we examined the presence of T. gondii within a range of tissues in sheep and cattle at 6 weeks and 6 months following oral infection with 10(3) or 10(5) sporulated oocysts of T. gondii. The presence of parasite was determined by bioassay in mice and using polymerase chain reaction (PCR). The results from this study show that T. gondii was more frequently and consistently detected in sheep, in particular within brain and heart tissues, whereas parasites were not detected in the samples of tissues taken from cattle. T. gondii was more frequently detected in sheep given the higher dose of T. gondii. Examination of tissues at either 6 weeks or 6 months after infection did not appear to affect the distribution of T. gondii. The polymerase chain reaction has more specificity and sensitivity when detecting the presence of T. gondii in large animals than histological detection. 相似文献
12.
The peroxidase-anti-peroxidase (PAP), avidin-biotin-complex (ABC) techniques, and electron microscopy, were used to identify protozoan parasites in formalin-fixed material from routine necropsy cases. The material comprised paraffin blocks, that had been stored for up to 18 years, from 18 cases of suspected toxoplasmosis and encephalitozoonosis. With the ABC method a higher dilution of primary antibody could be used than with the PAP method. However, with both methods, a distinct reaction occurred with appropriate dilutions. The age of the material did not seem to effect the result. Frequently, phagocytized and necrotic parasites were also stained. Gystozoites (bradyzoites) of T. gondii were stained faintly compared to the endozoites (tachyzoites). A Toxoplasma-like parasite from a dog did not react with anti-Toxoplasma serum, and ultrastructurally it proved to be consistent with an unidentified cyst-forming sporozoan parasite previously reported in dogs. Electron microscopy based on paraffin-embedded tissue, seems to be a valuable method for identification of protozoan parasites, and thus provide a supplement or alternative to the immunoperoxidase methods. 相似文献
13.
Toxoplasma gondii virulence is commonly determined by mortality rate of infected mice. Limited data showed that virulent T. gondii strains had increased parasite growth in mice compared to that of less virulent strains. To determine if this is a common phenomenon for a variety of strains and to develop an alternative assay to test acute virulence in mice, we measured parasite burdens in experimentally infected outbred CD-1 mice for 19 T. gondii isolates, in which the virulence phenotypes had previously been determined by mortality assay. Our results showed that parasite concentrations in spleen tissues were two orders of magnitude higher in the virulent than the intermediately and non-virulent isolates at day 7 post infection. In competition assays, mice inoculated with mixed tachyzoites of virulent and intermediately virulent strains or virulent and non-virulent strains showed that the former always reached a higher concentration at day 7 post infection. In mixed infection of intermediate and non-virulent strains, both strains were detectable in mice at day 7 post infection. In conclusion, our data showed that the virulence of T. gondii can be predicted by parasite load in the spleen tissue of infected mice at 7 days post infection, providing an alternative method to determine virulence of Toxoplasma. 相似文献
14.
Toxoplasma gondii rhomboid protein 1 (TgROM1) is a potential vaccine candidate against toxoplasmosis
Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The rhomboid proteins which are responsible for adhesion and invasion of host cells have been suggested as vaccine candidates against toxoplasmosis. A DNA vaccine (pVAX-ROM1) encoding T. gondii rhomboid protein 1 (TgROM1) gene was constructed and the immune response and protective efficacy of this vaccine against lethal challenge in BALB/c mice were evaluated. The results indicated that specific antibody and lymphocyte proliferative responses were elicited in mice receiving pVAX-ROM1. The production levels of IFN-γ, IL-2, IL-4, and IL-10, as well as the percentage of CD4(+) cells in mice vaccinated with pVAX-ROM1 were significantly increased respectively, compared to controls receiving either pVAX1 alone or PBS. After lethal challenge, the mice immunized with pVAX-ROM1 showed an increased survival time compared with the mice in the controls. Our data suggested that a DNA vaccine pVAX-ROM1 encoding T. gondii rhomboid protein 1 triggered strong humoral and cellular responses, and prolonged survival time against T. gondii infection in BALB/c mice. 相似文献
15.
Bokken GC van Eerden E Opsteegh M Augustijn M Graat EA Franssen FF Görlich K Buschtöns S Tenter AM van der Giessen JW Bergwerff AA van Knapen F 《Veterinary parasitology》2012,184(2-4):126-132
The aim of this study was to examine the dynamics of parasite specific antibody development in Trichinella spiralis and Toxoplasma gondii co-infections in pigs and to compare these with antibody dynamics in T. spiralis and T. gondii single infections. In this experiment, fifty-four pigs were divided into five inoculated groups of ten animals, and one control group of four animals. Two groups were inoculated with a single dose of either T. gondii tissue cysts or T. spiralis muscle larvae, one group was inoculated simultaneously with both parasites and two groups were successively inoculated at an interval of four weeks. Specific IgG responses to the parasites were measured by ELISA. T. gondii burden was determined by MC-PCR carried out on heart muscle and T. spiralis burden by artificial digestion of diaphragm samples. Specific IgG responses to T. gondii and T. spiralis in single and simultaneously inoculated animals showed a respective T. gondii and T. spiralis inoculation effect but no significant interaction of these parasites to the development of specific antibodies with the serum dilutions used. Moreover, our data showed that the specific IgG response levels in groups of animals successively or simultaneously co-infected were independent of a respective previous or simultaneous infection with the other parasite. Additionally, no differences in parasite burden were found within groups inoculated with T. gondii and within groups inoculated with T. spiralis. Conclusively, for the infection doses tested in this experiment, the dynamics of specific antibody development does not differ between single and simultaneous or successive infection with T. gondii and T. spiralis. However, lower parasitic doses and other ratios of doses, like low-low, low-high and high-low of T. gondii and T. spiralis in co-infection, in combination with other time intervals between successive infections may have different outcomes and should therefore be studied in further detail. 相似文献
16.
It was suspected that feline immunodeficiency virus (FIV) infection would affect the function of feline macrophages, and that the concomitant infection of cats with FIV and Toxoplasma gondii would cause even greater changes in macrophage function. Sixteen specific-pathogen-free kittens, four per group, were infected either with FIV, T. gondii, both pathogens, or neither pathogen. After the cats had been infected with FIV for 14 weeks (8 weeks after T. gondii infection), peritoneal macrophages were collected. Some macrophages were stimulated with lipopolysaccharide and supernatants were collected for the measurement of interleukin-1 production. Other macrophages were infected with T. gondii in a microbiocidal assay. Peritoneal macrophages from cats infected with FIV had decreased interleukin-1 secretion and increased antimicrobial activity. Co-infection with T. gondii apparently had no effect on these modifications of macrophage activity. Thus, acute FIV infection alone caused significant changes in macrophage functions that were not affected by concomitant T. gondii infection. 相似文献
17.
弓形虫P30基因及其功能 总被引：1，自引：0，他引：1
徐大刚 《中国兽医寄生虫病》2002,(3)
弓形虫 P30基因所编码的蛋白为弓形虫主要表面抗原 SAG1 ,其约占速殖子总蛋白量的 5 %,SAG1对虫体侵入宿主细胞及其毒力具重要性 ,并有高度免疫原性和免疫保护性 ,被用于弓形虫疫苗的研制和弓形虫感染的分子诊断 相似文献
18.
Toxoplasma gondii, a zoonotic protozoal parasite, is well-known for its global distribution and its ability to infect virtually all warm-blooded vertebrates. Nonetheless, attempts to describe the population structure of T. gondii have been primarily limited to samples isolated from humans and domesticated animals. More recent studies, however, have made efforts to characterize T. gondii isolates from a wider range of host species and geographic locales. These findings have dramatically changed our perception of the extent of genetic diversity in T. gondii and the relative roles of sexual recombination and clonal propagation in the parasite's lifecycle. In particular, identification of novel, disease-causing T. gondii strains in wildlife has raised concerns from both a conservation and public health perspective as to whether distinct domestic and sylvatic parasite gene pools exist. If so, overlap of these cycles may represent regions of high probability of disease emergence. Here, we attempt to answer these key questions by reviewing recent studies of T. gondii infections in wildlife, highlighting those which have advanced our understanding of the genetic diversity and population biology of this important zoonotic pathogen. 相似文献
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Buxton D Maley SW Wright SE Rodger S Bartley P Innes EA 《Veterinary parasitology》2007,149(1-2):25-28
Ovine toxoplasmosis, caused by the intracellular protozoan parasite Toxoplasma gondii, was first described in 1954 and while the incidence of ovine infection is difficult to define, it has been reported that in the UK it is responsible for between 1 and 2% of neonatal losses per annum. Recent reports have suggested that sheep persistently infected with T. gondii may pass infection to the fetus in subsequent pregnancies more readily than previously thought. These data show a high proportion of both successful and failed pregnancies in sheep to be positive by PCR for T. gondii with a tendency for samples from certain genetic lines of Charollais sheep more likely to be positive than samples from other lines, suggesting that some sheep have a particular genetic susceptibility to T. gondii. 相似文献