Home About us Contact
|
Home About us Contact | ||
|
|
||
Gondii
Kinds of Gondii Terms modified by Gondii Selected AbstractsActin-like protein 1 (ALP1) is a component of dynamic, high molecular weight complexes in Toxoplasma gondii,CYTOSKELETON, Issue 1 2010Jennifer L. Gordon Abstract Apicomplexan parasites, such as Toxoplasma gondii, rely on actin-based motility for cell invasion, yet conventional actin does not appear to be required for cell division in these parasites. Apicomplexans also contain a variety of actin-related proteins (Arps); however, most of these not directly orthologous to Arps in well-studied systems. We recently identified an apicomplexan-specific member of this family called Actin-Like Protein 1, (ALP1), which plays a role in the assembly of vesicular components recruited to the inner membrane complex (IMC) of daughter cells during cell division. In addition to its enrichment at daughter cell membranes, ALP1 is localized throughout the cytoplasm both diffusely distributed and concentrated in clusters that are detected by fluorescence microscopy, suggesting it forms complexes. Using quantitative optical imaging methods, including fluorescence recovery after photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP), we demonstrated that ALP1 is a component of a large complex, and that it readily exchanges between diffusible and complex-bound forms. Sedimentation and density gradient analyses revealed that ALP1 is found in a freely soluble state as well as high molecular weight complexes. During cell division, ALP1 was dynamically associated with the IMC, suggesting it rapidly cycles between freely diffusible and complex forms during daughter cell assembly. © 2009 Wiley-Liss, Inc. [source] Fine-needle aspiration cytology of subcutaneous toxoplasmosis: A case reportDIAGNOSTIC CYTOPATHOLOGY, Issue 10 2010Xiaowei Chen M.D. Abstract Toxoplasmosis is a common opportunistic infection in patients with AIDS in whom it typically presents as encephalitis, pneumonia, lymphadenitis, and myocarditis. Skin involvement is very rare and, to our best knowledge, Toxoplasma gondii forming a subcutaneous mass has not been reported. Here, we report the findings of an interesting case of subcutaneous toxoplasmosis with the cytological appearance of an inflammatory fibrovascular lesion in a HIV-positive patient and discuss the differential diagnosis. Diagn. Cytopathol. 2010;38:716,720. © 2009 Wiley-Liss, Inc. [source] Mice with neonatally induced inactivation of the vascular cell adhesion molecule-1 fail to control the parasite in Toxoplasma encephalitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2003Martina Deckert Abstract Under various inflammatory conditions, cell adhesion molecules are up-regulated in the central nervous system (CNS) and may contribute to the recruitment of leukocytes to the brain. In the present study, the functional role of vascular cell adhesion molecule (VCAM)-1 in Toxoplasma encephalitis (TE) was addressed using VCAMflox/flox MxCre mice. Neonatal inactivation of the VCAM-1 gene resulted in a lack of induction of VCAM-1 on cerebral blood vessel endothelial cells, whereas the constitutive expression of VCAM-1 on choroid plexus epithelial cells and the ependymawas unaffected; in these animals, resistance to T.,gondii was abolished, and VCAMflox/flox MxCre mice died of chronic TE caused by a failure to control parasites in the CNS. Although leukocyte recruitment to the CNS was unimpaired, the B cell response was significantly reduced as evidenced by reduced serum levels of anti- T.,gondii -specific IgM and IgG antibodies. Furthermore, the frequency and activation state of intracerebral T.,gondii -specific T cells were decreased, and microglial activation was markedly reduced. Taken together, these data demonstrate the crucial requirement of VCAM-1-mediated immune reactions for the control of an intracerebral infectious pathogen, whereas other cell adhesion molecules can efficiently compensate for VCAM-1-mediated homing across cerebral blood vessels. [source] Turning it on and off: regulation of dendritic cell function in Toxoplasma gondii infectionIMMUNOLOGICAL REVIEWS, Issue 1 2004Julio Aliberti Summary:, Because of its intrinsic virulence, Toxoplasma gondii induces a potent interleukin-12 (IL-12)-dependent cell-mediated immune response that shuts down the growth of the replicative tachyzoite stage, thus promoting host survival and successful transmission through predation. At the same time, this response must be tightly controlled to prevent lethality due to cytokine-mediated immunopathology. Evidence accumulated in recent years suggests that dendritic cells (DCs) play a major role in the initiation of IL-12-driven host resistance and that IL-12 synthesis by DCs is carefully regulated to avoid overproduction. In addition, this work has revealed a critical role for DCs in determining the highly polarized T-helper 1 (Th1)-type response triggered by the parasite. In this review, we summarize our current understanding of how DC function is initiated by Toxoplasma and how parasite-primed DCs drive Th1 effector choice. In addition, we discuss recent findings concerning the pathways responsible for endogenous regulation of DC IL-12 production during T. gondii infection. [source] BALB/c mice resistant to Toxoplasma gondii infection proved to be highly susceptible when previously infected with Myocoptes musculinus fur mitesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2007Áurea Welter Summary The immune response induced by Toxoplasma gondii is characterized by Th1 immune mechanisms. We previously demonstrated that C57BL/6 mice infested with Myocoptes musculinus and infected with T. gondii by intraperitoneal route undergo accelerated mortality according to Th2 immune mechanisms induced by the acarian. To evaluate whether infection with M. musculinus influences T. gondii -induced Th1 response in a resistant mouse lineage, BALB/c, which develops latent chronic toxoplasmosis in a way similar to that observed in immunocompetent humans, this study was done. The animals were infected with T. gondii ME-49 strain 1 month after M. musculinus infestation, being the survival and the immune response monitored. The double-infected displayed higher mortality rate if compared with the mono-infected mice. In addition, infection with M. musculinus changed the T. gondii -specific immune response, converting BALB/c host to a susceptible phenotype. Spleen cells had increased the levels of IL-4 in double-infected mice. This alteration was associated with severe pneumonia, encephalitis and wasting condition. In addition, a higher tissue parasitism was observed in double-infected animals. It can be concluded that infection with these two contrasting parasites, M. musculinus and T. gondii, may convert an immunocompetent host into a susceptible one, and such a host will develop severe toxoplasmosis. [source] Novel 2-hydrazino-pyrimidin-4(3H)-one derivatives as potential dihydrofolate reductase inhibitorsJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2010Mariam S. Degani Novel substituted 2-hydrazino-pyrimidin-4(3H)-one derivatives were synthesized and examined for their antifolate activity against DHFR from Pneumocystis carinii (pc), Toxoplasma gondii (tg), Mycobacterium avium (ma), and rat liver (rl). A novel, simple, and feasible methodology was developed for the synthesis of the titled compounds. Amongst these, compound 8 6-phenyl-2-(2-(1-(thiophen-2-yl) ethylidene)hydrazinyl) pyrimidin-4(3H)-one exhibited 17.74 ,M activity against pcDHFR. J. Heterocyclic Chem., (2010). [source] Synthesis of 2,6-diamino-5-[(2-substituted phenylamino)ethyl]pyrimidin-4(3h)-one as inhibitors of folate metabolizing enzymes,,JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 6 2006Aleem Gangjee A series of eleven novel 2,6-diamino-5-[(2-substituted phenylamino)ethyl]pyrimidin-4(3H)-one derivatives were synthesized as potential inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS). The synthesis of analogues 2a-f, 3a and 3e was achieved via an improved method. Commercially available anilines 12a-f were used as starting materials which on reaction with chloroacetaldehyde followed by cyanoacetate and cyclocondensation with guanidine afforded 2,6-diamino-5-[(2-substituted phenylamino)ethyl]pyrimidin-4(3H)-one 2a-f in three steps. The N-methyl analogues 3a-3e were prepared by reductive methylation. These compounds were evaluated against dihydrofolate reductase from Escherichia coli, Toxoplasma gondii, Pneumocystis carinii, human, and rat liver. Few compounds were marginally active against dihydrofolate reductase. The most potent inhibitor, (2c) which has a 1-naphthyl substituent on the side chain, has an IC50 = 150 ,M and 9.1 ,M against Escherichia coli and Toxoplasma gondii DHFR, respectively. [source] 7-Methyl Trimethoprim Analogues as Inhibitors of the Folate Metabolizing Enzymes,JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2003Aleem Gangjee A series of 5-(1-phenylethyl)pyrimidines 2,10 (Table I) were designed and synthesized as potent and selective inhibitors of Pneumocystis carinii (P. carinii), Toxoplasma gondii (T. gondii) and Mycobacterium avium (M. avium) dihydrofolate reductases (DHFR). The structure of 2,10 incorporates a 7-methyl group to increase the potency of monocyclic trimethoprim (TMP). The target compounds were synthesized by an acid catalyzed condensation of ethyl cyanoacetate and appropriately substituted benzaldehydes followed by a Michael addition using methyl copper-lithium. The resulting adduct was cyclocondensed with guanidine to afford 2,6-diamino-4-hydroxy-5-(1-phenylethyl)pyrimidines 2,7. Both amino moieties of 2,4 were protected with pivaloyl groups and their 4-hydroxy group chlorinated with phosphorus oxychloride. The resulting intermediates were subjected to hydrogenation and deprotection to afford 8,10. Compound 7 was a good inhibitor of DHFR, however the other compounds were poor inhibitors of P. carinii, T. gondii and M. avium DHFR. [source] Synthesis of 2,4-diaminopyrido[2,3- d]pyrimidines and 2,4-diamino-quinazolines with bulky dibenz[b,f]azepine and dibenzo[a,d]-cycloheptene substituents at the 6-position as inhibitors of dihydrofolate reductases from pneumocystis carinii, toxoplasma gondii, and mycobacterium avium,JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2000Andre Rosowsky The synthesis of four previously undescribed 2,4-diaminopyrido[2,3- d]pyrimidines (3,4) and 2,4-diaminoquinazolines (5,6) with a bulky tricyclic aromatic group at the 6-position is described. Condensation of dibenz[b,f]azepine with 2,4-diamino-6-bromomethylpyrido[2,3- d]pyrimidine (8) and 2,4-diamino-6-bromomethylquinazoline (17) in the presence of sodium hydride afforded N -[(2,4-diaminopyrido[2,3- d]-pyrimidin-6-yl)methyl]dibenz[b,f]azepine (3) and N -[(2,4-diaminoquinazolin-6-yl)methyl]dibenz[b,f]-azepine (4), respectively. Condensation of 5-chlorodibenzo[a,d]cycloheptene (19) and 5-chloro-10,11-dihydrodibenzo[a,d]cycloheptene (20) with 2,4,6-triaminoquinazoline (13) afforded 5-[(2,4-diamino-quinazolin-6-yl)amino]-5H -dibenzo[a,d]cycloheptene (5) and the corresponding 10,11-dihydro derivative (6), respectively. The bromides 8 and 17, as hydrobromic acid salts, were obtained from the corresponding nitriles according to a standard three-step sequence consisting of treatment with Raney nickel in formic acid followed by reduction with sodium borohydride and bromination with dry hydrogen bromide in glacial acetic acid. Compounds 3,6 were evaluated in vitro for the ability to inhibit dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. Compounds 3 and 4 were potent inhibitors of all four enzymes, with IC50 values in the 0.03,0.1 ,M range, whereas 5 was less potent. However the selectivity of all four compounds for the parasite enzymes relative to the rat enzyme was<10-fold, whereas the recently reported lead compound in this series, N -[(2,4-diaminopteridin-6-yl)methyl]dibenz[b,f]azepine (1) has > 100-fold selectivity for the T. gondii and M. avium enzyme and 21-fold selectivity for the P carinii enzyme. [source] Toxoplasma gondii, HCV, and HBV seroprevalence and co-infection among HIV-positive and -negative pregnant women in Burkina FasoJOURNAL OF MEDICAL VIROLOGY, Issue 6 2006Jacques Simpore Abstract Toxoplasma gondii (T. gondii) infections can cause serious complications in HIV-infected pregnant women, leading to miscarriage, stillbirth, birth defects (e.g., mental retardation, blindness, epilepsy etc.) and could favor or enhance the mother-to-child transmission of HCV, HBV, and HIV vertical transmission. From May 20, 2004 to August 3, 2005, 336 18,45 years aged pregnant women, were enrolled for an investigation of the prevalence of serum antibodies against T. gondii, HCV, HBV, and HIV using ELISA. The prevalence of T. gondii, HCV, and HBV in pregnant women was 25.3%, 5.4%, and 9.8%, respectively and the HIV serostatus (61.6%) seems to be associated with greater prevalence rates of both T. gondii (28.5% vs. 20.2%) and HBV (11.6% vs. 7.0%). Without taking into account HIV, only 65.5% (220 of 336) of the women were not infected with these agents. The co-infection rate between HIV-infected and -negative women was different statistically: T. gondii/HBV 0.048 versus 0.015, T. gondii/HCV 0.014 versus 0.008, and HCV/HBV 0.005 versus 0.008, respectively. The elevated co-infection rate in HIV-positive women demonstrated that they are exposed to T. gondii, HCV, and HBV infections prevalently by sexual contact. J. Med. Virol. 78:730,733, 2006. © 2006 Wiley-Liss, Inc. [source] Neosporosis and hammondiosis in dogsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 6 2007M. P. Reichel The dog is a definitive host of the protozoan parasite Neospora caninum, and in many parts of the world, infection is relatively common as determined by serology. Reported seroprevalences usually range from 0 to 20 per cent, however, reports of clinically affected dogs are infrequent. Affected dogs are generally less than six months old and predominantly have signs of an ascending hindleg paralysis, with the associated lesions of polyradiculoneuritis and granulomatous polymyositis. Although any organ may be affected, infections are more common in the central nervous system, muscles, lungs and skin. Ante-mortem diagnosis is difficult but serology and cytology can aid diagnosis. The diagnosis can be confirmed by histology, immunohistochemistry, the use of molecular techniques on biopsy material, or on post-mortem examination. Neospora caninum oocysts are rarely found in faeces and must be differentiated from oocysts of related coccidians such as Hammondia heydorni and Toxoplasma gondii. Hammondia heydorni can cause diarrrhoea in immunosuppressed dogs. Neosporosis should be suspected in young pups with an ascending paralysis of the hindlegs. Treatment with clindamycin and potentiated sulphonamides may be useful in cases where muscular atrophy and fibrosis are absent. Feeding of raw meat is a potential risk factor for infection of dogs and should be discouraged. [source] Infectious Mononucleosis,Like Syndromes in Febrile Travelers Returning From the TropicsJOURNAL OF TRAVEL MEDICINE, Issue 4 2006Emmanuel Bottieau MD Background Infectious mononucleosis (IM), resulting from Epstein,Barr virus (EBV) infection, and IM-like syndromes, mainly due to cytomegalovirus (CMV), Toxoplasma gondii, or human immunodeficiency virus (HIV), have been occasionally reported in travelers returning from the tropics. Our objective was to investigate the prevalence, outcome, and diagnostic predictors of these syndromes in febrile travelers. Methods Between April 2000 and March 2005, all febrile travelers and migrants presenting at our referral centers within 12 months after a tropical stay were prospectively included. We identified all patients serologically diagnosed with IM or IM-like syndrome and compared them with the rest of the cohort. Results During the 5-year period, 72/1,842 patients (4%) were diagnosed with an IM-like syndrome, including 36 CMV, 16 T gondii, 15 EBV, and 5 HIV primary infections. All patients were western travelers or expatriates. Mean delay before consultation was 2 weeks. Most patients had consulted other practitioners and/or received presumptive treatment. A minority of patients presented with IM clinical features. Lymphocytosis ,40% of the white blood cells (WBC) and reactive/atypical lymphocyte morphology were observed in 60 and 30% of the patients. The four diseases were indistinguishable. Protracted fever and asthenia were common but complications rarely occurred. IM-like syndromes were independently associated with fever >7 days, lymphadenopathy, elevated liver enzymes, and lymphocytosis ,40% of WBC. Diagnostic probability increased to >20% if at least three of these predictors were present. Conclusions Diagnosis of IM and IM-like syndrome is not uncommon in febrile travelers, with a higher proportion of primary CMV, T gondii, and HIV infections than in nonimported series. Consequently, classic IM clinical and laboratory features are often lacking. All four pathogens should be systematically considered because early diagnosis should avoid unnecessary investigations and treatment and allow early intervention in case of primary HIV infection. [source] Evaluation and applicability of a purification method coupled with nested PCR for the detection of Toxoplasma oocysts in waterLETTERS IN APPLIED MICROBIOLOGY, Issue 5 2006C. Kourenti Abstract Aims:, To describe the development, evaluation and applicability of a complete method for the detection of Toxoplasma gondii in water. Methods and Results:, The method incorporated concentration of water samples by Al2(SO4)3 -flocculation, purification by discontinuous sucrose gradients and detection of toxoplasmic DNA by 18S-rRNA nested PCR. Tap water replicates and natural water samples were seeded with defined numbers of Toxoplasma oocysts and processed for evaluation studies. When applied to environmental samples, the method gave highest detection sensitivities of 100 oocysts in river water and 10 oocysts in well- and sea water. The method was finally applied in 60 water samples of different quality and origin collected over a 14-month period. Toxoplasmic DNA was detected in four samples. Conclusions:, The method offers an alternative towards improving current methods that can be used for the detection of Toxoplasma oocysts in environmental water samples. Significance and Impact of the Study:, The method in its current form will be helpful for assessment of Toxoplasma contamination in water resources, particularly after outbreak events. [source] Specific IgE to allergens in cord blood is associated with maternal immunity to Toxoplasma gondii and rubella virusALLERGY, Issue 11 2008M. J. Ege Background:, Various studies have found reduced prevalences of atopic sensitization and atopic diseases in children previously exposed to infections or living conditions with a high microbial burden, such as the farming environment. Objective:, We sought to determine the relationships of cord blood immunoglobulin E (IgE) with maternal health conditions before and during pregnancy. Methods:, Pregnant women living in rural areas in five European countries were recruited in the third trimester of pregnancy. Information on maternal health during pregnancy was collected from maternity records and by questionnaires (n = 497). Specific IgE for inhalant and food allergens was assessed in cord blood and peripheral blood samples of the mothers. Results:, Inverse associations of cord blood IgE to seasonal allergens with positive maternal records for Toxoplasma gondii (adjusted odds ratio = 0.37 [0.17,0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13,0.96]) were found. The previously described effect of prenatal farm exposure on IgE to seasonal allergens was partly confounded by a positive maternal record for T. gondii. The number of maternal siblings, maternal contact to cats during pregnancy or during her first year of life, predicted a positive maternal record for T. gondii. Conclusions:, Maternal immunity to T. gondii and rubella may impact on atopic sensitization in the fetus. A positive T. gondii record explained the previously identified effect of prenatal farm exposure on IgE to seasonal allergens only to a minor extent. [source] Isolation and characterization of microsatellite markers from Sarcocystis neurona, a causative agent of equine protozoal myeloencephalitisMOLECULAR ECOLOGY RESOURCES, Issue 1 2006INGRID M. ASMUNDSSON Abstract The population genetics and systematics of coccidian parasites of the genus Sarcocystis remain poorly defined, notwithstanding their relevency to veterinary and human health. Despite opportunities for sexual recombination, nonrecombinant parasite clones characterized by distinct transmission and pathogenesis traits persist in related parasites (i.e. Toxoplasma gondii). In order to determine whether this may be generally true for parasitic coccidia, and to address evolutionary and taxonomic problems within the genus Sarcocystis, we isolated 12 polymorphic microsatellite markers (four to 14 alleles) for Sarcocystis neurona, the major causative agent of equine protozoal myeloencephalitis (EPM). [source] Cathepsin L occupies a vacuolar compartment and is a protein maturase within the endo/exocytic system of Toxoplasma gondiiMOLECULAR MICROBIOLOGY, Issue 6 2010Fabiola Parussini Summary Regulated exocytosis allows the timely delivery of proteins and other macromolecules precisely when they are needed to fulfil their functions. The intracellular parasite Toxoplasma gondii has one of the most extensive regulated exocytic systems among all unicellular organisms, yet the basis of protein trafficking and proteolytic modification in this system is poorly understood. We demonstrate that a parasite cathepsin protease, TgCPL, occupies a newly recognized vacuolar compartment (VAC) that undergoes dynamic fragmentation during T. gondii replication. We also provide evidence that within the VAC or late endosome this protease mediates the proteolytic maturation of proproteins targeted to micronemes, regulated secretory organelles that deliver adhesive proteins to the parasite surface during cell invasion. Our findings suggest that processing of microneme precursors occurs within intermediate endocytic compartments within the exocytic system, indicating an extensive convergence of the endocytic and exocytic pathways in this human parasite. [source] Congenital toxoplasmosis: late pregnancy infections detected by neonatal screening and maternal serological testing at deliveryPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 6 2007Eleonor G. Lago Summary The first aim of this study was to determine the prevalence of congenital toxoplasmosis in newborn infants treated by the public health system in Porto Alegre, a city in southern Brazil, using neonatal screening for Toxoplasma gondii -specific IgM. The second aim was to investigate whether the cases detected by this approach could have been identified by the prenatal screening for antibodies to T. gondii that was performed in the same population. A fluorometric assay was used to analyse T. gondii -specific IgM in filter paper specimens obtained from newborn infants for routine screening for metabolic diseases. When the specific IgM was positive, serum samples from the infant and the mother were requested for confirmatory serological testing, and the infant underwent clinical examination. Among 10 000 infants screened for T. gondii -specific IgM, seven filter paper samples were positive, and congenital toxoplasmosis was confirmed in six patients. The prevalence of IgM specific for T. gondii was 6/10 000 [95% CI 2/10 000, 13/10 000]. One infected infant had already been identified in the maternity ward before birth, three had been identified by maternal serology at delivery, and two infants with congenital toxoplasmosis were identified solely through neonatal screening. Although four mothers of the patients with congenital toxoplasmosis received prenatal care, and three mothers had one or two serological tests for T. gondii -specific antibodies (one at first trimester, one at first and second trimesters, and the other at second and third trimesters), they were not identified during pregnancy as infected. Neonatal screening identified cases of infection not detected by obtaining only one or two serum samples from pregnant women for T. gondii serology, mainly when infection was acquired and transmitted in late pregnancy. Maternal serology at delivery and neonatal screening were especially useful in the identification of infants with congenital toxoplasmosis when the mother did not receive regular prenatal serological testing or prenatal care. [source] Control of Toxoplasma gondii infection by athymic LEW- Whnrnu ratsPARASITE IMMUNOLOGY, Issue 6-7 2008J. C. SEPULVEDA-ARIAS SUMMARY In immunocompetent rats and humans infection with Toxoplasma gondii remains mostly without overt clinical symptoms, but can be fatal, if the T-cell response is impaired. For a better understanding of the lack of control of T. gondii infection under immunosuppressed conditions, congenitally athymic rats were used as the experimental model. Whereas athymic F344- Whnrnu (F344 nude) rats die from a generalized infection during the first 3 weeks after peritoneal inoculation with 106 tachyzoites of T. gondii strain NTE, LEW- Whnrnu (LEW nude) rats and euthymic LEW rats infected with a 10-fold higher number of parasites developed chronic infection. To identify underlying mechanisms of LEW rats resistance to T. gondii infection and to investigate a possible contribution of residual T-cells to LEW- Whnrnu rat resistance, we characterized the immune response of LEW rats by determination of cellularity and composition of lymphocyte population, antigen-specific IgG2b response as well as assays of antigen-specific proliferation and production of IL-2, IFN-, and TNF-,. As only euthymic LEW rats developed production of antigen-specific IgG and cellular in vitro responses, these results strongly suggest that the genetic background of LEW rats permits a control of the infection independent of an adaptive immune response. [source] GRA7 provides protective immunity in cocktail DNA vaccines against Toxoplasma gondiiPARASITE IMMUNOLOGY, Issue 9 2007E. JONGERT SUMMARY In a previous study, single-gene vaccination with GRA1, GRA7 or ROP2 was shown to elicit partial protection against Toxoplasma gondii. In this study, the contribution of each antigen in the evoked humoral and cellular immune responses was evaluated after vaccination with plasmid mixtures containing GRA1, GRA7 and ROP2. Cocktail DNA vaccinated mice developed high antibody titers against the antigens from two-gene DNA vaccine cocktails, but lower titres when immunized with the three-gene cocktail. High numbers of IFN-, secreting splenocytes were generated predominantly against GRA7. Brain cyst burden was reduced by 81% in mice vaccinated with the three-gene mixture and they were completely protected against acute toxoplasmosis. Similar high levels of brain cyst reductions were obtained after vaccination with cocktails composed of GRA1 and GRA7 (89% reduction), or GRA7 and ROP2 (79% reduction), but not with the cocktail composed of GRA1 and ROP2. In low dose single-gene vaccinations, IFN-, and strong protection could only be elicited by GRA7. Hence, the presence of GRA7 in the DNA vaccine formulation was important for optimal protection and this was correlated with GRA7-specific IFN-, production. We propose GRA7 as a main component in cocktail DNA vaccines for vaccination against T. gondii. [source] Ocular toxoplasmosis: in the storm of the eyePARASITE IMMUNOLOGY, Issue 12 2006L. A. JONES SUMMARY Ocular toxoplasmosis (OT) can occur in the children of mothers infected with Toxoplasma gondii during pregnancy. It is not limited to the congenitally infected, but can also occur following adult-acquired infection or as a result of disease reactivation in immune-compromised and pregnant individuals. Many aspects of immune privilege in the eye, including constitutive TGF-, expression and reduced MHC class 1 expression, would appear at first to favour parasite survival. Conversely, many of the mechanisms that control parasite multiplication in other anatomical sites, such as nitric oxide expression, IFN-, and TNF-,, are known to disrupt immune privilege and are associated with ocular damage. Taking into account the opposing needs of limiting parasite multiplication and minimizing tissue destruction we review the pathogenesis of OT in the murine model. [source] Protecting babies: vaccine strategies to prevent foetopathy in Neospora caninum -infected cattlePARASITE IMMUNOLOGY, Issue 3 2006Review Article SUMMARY Neospora caninum is an apicomplexan protozoan parasite that is a significant infectious abortifacient agent in cattle. Despite the fact that it is a member of a well described taxonomic group, it is a relatively newly discovered parasite and its biology is not yet fully understood. Cattle become infected either congenitally via transplacental transmission or post-natally by ingesting oocysts derived from the definitive host; dogs and coyotes are the only definitive hosts that have been described to date. It is not known which of these two forms of transmission occurs most frequently and which is the most likely to result in abortion; there are no drugs available to treat infected cattle, so current control strategies rely on prevention of infection by management methods and strict hygiene; an effective vaccine would be a great advantage in its control. Neospora caninum is an economically important veterinary pathogen, but we can also draw analogies between its foetopathic effects and those of human pathogens such as Toxoplasma gondii, Chlamydophila abortus and Plasmodium falciparum. Understanding the immune response and the materno,foetal relationship in N. caninum -infected cattle may help us to design vaccination strategies, not only for neosporosis but also for other foetopathic agents. [source] CpG-containing ODN has a limited role in the protection against Toxoplasma gondiiPARASITE IMMUNOLOGY, Issue 2 2004R. Saavedra SUMMARY Bacterial DNA containing immunostimulatory motifs (CpG) induces the development of a TH1 immune response. Since protection against Toxoplasma gondii is correlated with this type of response, the aim of this work was to determine if a synthetic oligodeoxynucleotide (ODN) containing CpG sequences could be useful as adjuvant for the induction of a long-lasting protective immune response against T. gondii. BALB/c mice immunized with a total soluble antigen of T. gondii (TSA2) mixed with ODN-containing CpG sequences developed a typical TH1 response, as determined by antibody isotypes and interferon-, (IFN-,) and interleukin-4 (IL-4) production by spleen cells. However, they did not resist a challenge with the virulent RH strain of the parasite. Absence of protection paralleled with lower levels of IFN-,, when compared with mice vaccinated with the live tachyzoites of the attenuated ts.4 strain of the parasite, which resisted this challenge. Intraperitoneal injection of ODN alone to mice induced a high degree of resistance to a lethal challenge inoculated by the same route. Nevertheless, this nonspecific protection was transient. Thus, the use of ODN containing CpG motifs as adjuvant is of limited value for the induction of a protective immune response against T. gondii. [source] A previous infection with Toxoplasma gondii does not protect against a challenge with Neospora caninum in pregnant sheepPARASITE IMMUNOLOGY, Issue 3 2001E.A. Innes Sheep immunized with Toxoplasma gondii (Toxovax®) prior to pregnancy were tested for their ability to withstand a challenge at 90 days gestation with 107 Neospora caninum (NC1) tachyzoites. The antibody responses in sheep following immunization with T. gondi were specific for T. gondii whereas peripheral blood mononuclear cells responded to both T. gondii and caninum antigen in vitro. This suggested that there was induction of crossreactive immune recognition in the sheep, at least at the cellular level. Following challenge of sheep at mid-gestation with N caninum, no febrile responses were recorded in the group of sheep which had previously received Toxovax® while significant febrile responses were recorded in the group of sheep which received N challenge alone. Antibody responses to N developed in all sheep following challenge and antibody responses to T,gondii were boosted in the group of sheep which had previously been immunized with Toxovax®. No antibodies to were observed in the sheep which received the challenge alone. Peripheral blood mononuclear cells from both groups of sheep responded to T.gondii N.caninum antigen invitro and interferon gamma was present in the cell-free supernatant from activated cells. However despite evidence of the induction of crossreactive immunity between T.gondii N.caninum this was not sufficient to prevent foetal death. The group of sheep which had received Toxovax® prior to pregnancy and the group of sheep which only received the N.caninum challenge experienced 100% foetal death compared with 0% in the unchallenged control group. Vaccination prior to pregnancy with Toxovax® did protect against foetal death following oral challenge at 90 days with 2000 oocysts which caused 100% foetal death in a control challenge group. [source] HIV-associated opportunistic pneumoniasRESPIROLOGY, Issue 4 2009Laurence HUANG ABSTRACT Among the HIV-associated pulmonary complications, opportunistic pneumonias are major causes of morbidity and mortality. The spectrum of HIV-associated opportunistic pneumonias is broad and includes bacterial, mycobacterial, fungal, viral and parasitic pneumonias. Bacterial pneumonia is the most frequent opportunistic pneumonia in the United States and Western Europe while tuberculosis is the dominant pathogen in sub-Saharan Africa. With the use of combination antiretroviral therapy and prophylaxis, the incidence of Pneumocystis pneumonia (PCP) has declined. Nevertheless, PCP continues to occur in persons who are unaware of their HIV infection, those who fail to access medical care, and those who fail to adhere to antiretroviral therapy or prophylaxis. Although pneumonias due to Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, cytomegalovirus and Toxoplasma gondii are less frequent, their presence in the lung is often indicative of disseminated disease and is associated with significant mortality. [source] The Role of Acidocalcisomes in Parasitic Protists,THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 3 2009SILVIA N. J. MORENO ABSTRACT. Acidocalcisomes are acidic organelles with a high concentration of phosphorus present as pyrophosphate (PPi) and polyphosphate (poly P) complexed with calcium and other cations. The acidocalcisome membrane contains a number of pumps (Ca2+ -ATPase, V-H+ -ATPase, H+ -PPase), exchangers (Na+/H+, Ca2+/H+), and channels (aquaporins), while its matrix contains enzymes related to PPi and poly P metabolism. Acidocalcisomes have been observed in pathogenic, as well as non-pathogenic prokaryotes and eukaryotes, e.g. Chlamydomonas reinhardtii, and Dictyostelium discoideum. Some of the potential functions of the acidocalcisome are the storage of cations and phosphorus, the participation of phosphorus in PPi and poly P metabolism, calcium homeostasis, maintenance of intracellular pH homeostasis, and osmoregulation. In addition, acidocalcisomes resemble lysosome-related organelles (LRO) from mammalian cells in many of their properties. For example, we found that platelet dense granules, which are LROs, are very similar to acidocalcisomes. They share a similar size, acidic properties, and both contain PPi, poly P, and calcium. Recent work that indicates that they also share the system for targeting of their membrane proteins through adaptor protein 3 reinforces this concept. The fact that acidocalcisomes interact with other organelles in parasitic protists, e.g. the contractile vacuole in Trypanosoma cruzi, and other vacuoles observed in Toxoplasma gondii, suggests that these cellular compartments may be associated with the endosomal/lysosomal pathway. [source] The History of Toxoplasma gondii,The First 100 YearsTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 6 2008JITENDER P. DUBEY ABSTRACT. In this paper the history of Toxoplasma gondii and toxoplasmosis is reviewed. This protozoan parasite was first discovered in 1908 and named a year later. Its medical importance remained unknown until 1939 when T. gondii was identified in tissues of a congenitally infected infant, and veterinary importance became known when it was found to cause abortion storms in sheep in 1957. The discovery of a T. gondii specific antibody test, Sabin,Feldman dye test in 1948 led to the recognition that T. gondii is a common parasite of warm-blooded hosts with a worldwide distribution. Its life cycle was not discovered until 1970 when it was found that felids are its definitive host and an environmentally resistant stage (oocyst) is excreted in feces of infected cats. The recent discovery of its common infection in certain marine wildlife (sea otters) indicates contamination of our seas with T. gondii oocysts washed from land. Hygeine remains the best preventive measure because currently there is no vaccine to prevent toxoplasmosis in humans. [source] How Epigenomics Contributes to the Understanding of Gene Regulation in Toxoplasma gondii,THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 6 2008MATHIEU GISSOT ABSTRACT. How apicomplexan parasites regulate their gene expression is poorly understood. The complex life cycle of these parasites implies tight control of gene expression to orchestrate the appropriate expression pattern at the right moment. Recently, several studies have demonstrated the role of epigenetic mechanisms for control of coordinated expression of genes. In this review, we discuss the contribution of epigenomics to the understanding of gene regulation in Toxoplasma gondii. Studying the distribution of modified histones on the genome links chromatin modifications to gene expression or gene repression. In particular, coincident trimethylated lysine 4 on histone H3 (H3K4me3), acetylated lysine 9 on histone H3 (H3K9ac), and acetylated histone H4 (H4ac) mark promoters of actively transcribed genes. However, the presence of these modified histones at some non-expressed genes and other histone modifications at only a subset of active promoters implies the presence of other layers of regulation of chromatin structure in T. gondii. Epigenomics analysis provides a powerful tool to characterize the activation state of genomic loci of T. gondii and possibly of other Apicomplexa including Plasmodium or Cryptosporidium. Further, integration of epigenetic data with expression data and other genome-wide datasets facilitates refinement of genome annotation based upon experimental data. [source] Recombinant proteins in the diagnosis of toxoplasmosisAPMIS, Issue 8 2010DUPADAHALLI KOTRESHA Kotresha D, Rahmah N. Recombinant proteins in the diagnosis of toxoplasmosis. APMIS 2010; 118: 529,42. Toxoplasma gondii is an important human pathogen with a worldwide distribution. It is primarily of medical importance for pregnant women and immunocompromised patients. Primary infection of the former is often associated with fetal infection, which can lead to abortion or severe neonatal malformation. Immunocompromised patients are at risk of contracting the severe form of the disease that may be fatal. Thus, detection of T. gondii infection with high sensitivity and specificity is crucial in the management of the disease. Toxoplasmosis is generally diagnosed by demonstrating specific immunoglobulin M (IgM) and IgG antibodies to toxoplasma antigens in the patient's serum sample. Most of the commercially available tests use T. gondii native antigens and display wide variations in test accuracy. Recombinant antigens have great potential as diagnostic reagents for use in assays to detect toxoplasmosis. Thus in this review, we address recent advances in the use of Toxoplasma recombinant proteins for serodiagnosis of toxoplasmosis. [source] Monocytes/macrophages infected with Toxoplasma gondii do not increase co-stimulatory molecules while maintaining their migratory abilityAPMIS, Issue 9 2009DANIELE SEIPEL Toxoplasma gondii is 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 and use them for dispersal throughout the body, but the activation state of those cells is unknown. We investigated the ability of human and murine cells from monocytic/macrophage lineages that had not previously been exposed to inflammatory cytokines to up-regulate co-stimulatory and adhesion molecules upon infection. Toxoplasma gondii -infected human monocytes (freshly isolated and THP1 lineage) were unable to up-regulate CD86, CD83, CD40 or CD1a. CD80 expression increased in infected cells but expression of l -selectin and ,2 integrin was unaltered. We evaluated the ability of infected macrophages from wild type C57/BL/6 or CD14,/, mice to migrate in 8 ,m transwells. Infected cells from CD14,/, mice were more likely to de-adhere than infected cells from wild type mice but they did not show any increase in migratory ability. The non-stimulatory profile of these infected cells may contribute to parasite spread throughout the lymphatic circulation in the initial phases of infection. [source] Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulenceAPMIS, Issue 5-6 2009IRA J. BLADER Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect most warm-blooded animals and cause severe and life-threatening disease in developing fetuses and in immune-compromised patients. Although Toxoplasma was discovered over 100 years ago, we are only now beginning to appreciate the importance of the role that parasite modulation of its host has on parasite growth, bradyzoite development, immune evasion, and virulence. The goal of this review is to highlight these findings, to develop an integrated model for communication between Toxoplasma and its host, and to discuss new questions that arise out of these studies. [source] | |||||||||||||||||||||||||||||||