Sunday, May 31, 2009

Does Toxoplasma gondii Infection Affect the Levels of IgE and Cytokines (IL-5, IL-6, IL-10, IL-12, and TNF-alpha)?

Clin Dev Immunol. 2009;2009:374696. Epub 2009 May 25

Does Toxoplasma gondii Infection Affect the Levels of IgE and Cytokines (IL-5, IL-6, IL-10, IL-12, and TNF-alpha)?

Matowicka-Karna J, Dymicka-Piekarska V, Kemona H.

Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, J. Waszyngton'a 15A, 15-269 Bialystok, Poland.

In the study performed in a group of patients infected with T. gondii, we evaluated Th2 humoral response (IL-5, IL-6, IL-10) and Th1 cell response (IL-12, TNF-alpha). The study objective was to assess the effect of T. gondii on chosen indices of the immune response. The study involved 52 women infected with T. gondii (aged 18-42 years) prior to antiparasitic treatment. In all the patients, we found IgM (index >0.7) and IgG which exceeded 300 IU/ml. The control group (C) consisted of 40 healthy women aged 18-46 years. In the study group (T) and in the control group (C), the levels of IgE, IL-5, IL-6, IL-10, IL-12, and TNF-alpha were determined. In our study, T. gondii patients had twofold higher levels of IL-5 and IL-6 as compared to healthy subjects, which seems to confirm the presence of an inflammatory state. We found the level of IL-10 to be fivefold higher in the course of toxoplasmosis than in healthy controls. The levels of IL-12 and TNF-alpha were comparable to those observed in healthy controls. The study has revealed that patients infected with T. gondii show increased production of the humoral response cytokines, whereas the generation of the cell response cytokines remains unchanged.

PMID: 19478959 [PubMed - in process]

Immunological Interactions between 2 Common Pathogens, Th1-Inducing Protozoan Toxoplasma gondii and the Th2-Inducing Helminth Fasciola hepatica

PLoS ONE. 2009 May 25;4(5):e5692

Immunological Interactions between 2 Common Pathogens, Th1-Inducing Protozoan Toxoplasma gondii and the Th2-Inducing Helminth Fasciola hepatica

Miller CM, Smith NC, Ikin RJ, Boulter NR, Dalton JP, Donnelly S.

Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, New South Wales, Australia.

BACKGROUND: The nature of the immune response to infection is dependent on the type of infecting organism. Intracellular organisms such as Toxoplasma gondii stimulate a Th1-driven response associated with production of IL-12, IFN-gamma, nitric oxide and IgG2a antibodies and classical activation of macrophages. In contrast, extracellular helminths such as Fasciola hepatica induce Th2 responses characterised by the production of IL-4, IL-5, IL-10 and IgG1 antibodies and alternative activation of macrophages. As co-infections with these types of parasites commonly exist in the field it is relevant to examine how the various facets of the immune responses induced by each may influence or counter-regulate that of the other. PRINCIPAL FINDINGS: Regardless, of whether F. hepatica infection preceded or succeeded T. gondii infection, there was little impact on the production of the Th1 cytokines IL-12, IFN-gamma or on the development of classically-activated macrophages induced by T. gondii. By contrast, the production of helminth-specific Th2 cytokines, such as IL-4 and IL-5, was suppressed by infection with T. gondii. Additionally, the recruitment and alternative activation of macrophages by F. hepatica was blocked or reversed by subsequent infection with T. gondii. The clinical symptoms of toxoplasmosis and the survival rate of infected mice were not significantly altered by the helminth. CONCLUSIONS: Despite previous studies showing that F. hepatica suppressed the classical activation of macrophages and the Th1-driven responses of mice to bystander microbial infection, as well as reduced their ability to reject these, here we found that the potent immune responses to T. gondii were capable of suppressing the responses to helminth infection. Clearly, the outcome of particular infections in polyparasitoses depends on the means and potency by which each pathogen controls the immune response.

PMID: 19478853 [PubMed - in process]

Friday, May 29, 2009

Increased incidence of traffic accidents in Toxoplasma-infected military drivers

BMC Infect Dis. 2009 May 26;9(1):72. [Epub ahead of print]

Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study

Flegr J, Klose J, Novotna M, Berenreitterova M, Havlicek J.

ABSTRACT: BACKGROUND: Latent toxoplasmosis, protozoan parasitosis with prevalence rates from 20 to 60 % in most populations, is known to impair reaction times in infected subjects, which results, for example, in a higher risk of traffic accidents in subjects with this life-long infection. Two recent studies have reported that RhD-positive subjects, especially RhD heterozygotes, are protected against latent toxoplasmosis-induced impairment of reaction times. In the present study we searched for increased incidence of traffic accidents and for protective effect of RhD positivity in 3890 military drivers. METHODS: Male draftees who attended the Central Military Hospital in Prague for regular entrance psychological examinations between 2000 and 2003 were tested for Toxoplasma infection and RhD phenotype at the beginning of their 1 to1.5-year compulsory military service. Subsequently, the data on Toxoplasma infection and RhD phenotype were matched with those on traffic accidents from military police records and the effects of RhD phenotype and Toxoplasma infection on probability of traffic accident was estimated with logistic regression. RESULTS: We confirmed, using for the first time a prospective cohort study design, increased risk of traffic accidents in Toxoplasma-infected subjects and demonstrated a strong protective effect of RhD positivity against the risk of traffic accidents posed by latent toxoplasmosis. Our results show that RhD-negative subjects with high titers of anti-Toxoplasma antibodies had a probability of a traffic accident of about 16.7 %, i.e. a more than six times higher rate than Toxoplasma-free or RhD-positive subjects. CONCLUSIONS: Our results showed that a common infection by Toxoplasma gondii could have strong impact on the probability of traffic accident in RhD negative subjects. The observed effects could provide not only a clue to the long-standing evolutionary enigma of the origin of RhD polymorphism in humans (the effect of balancing selection), but might also be the missing piece in the puzzle of the physiological function of the RhD molecule.

PMID: 19470165 [PubMed - as supplied by publisher]

Wednesday, May 27, 2009

Psychosis may be associated with toxoplasmosis

Med Hypotheses. 2009 May 19. [Epub ahead of print]

Psychosis may be associated with toxoplasmosis

Zhu S, Lun ZR.

Department of Microbiology and Immunology, College of Basic Medical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou, Henan 450001, PR China.

Many parasites induce characteristic changes in their host. The effect of Toxoplasma gondii infection on the cerebrum and neuropsychiatric patients has been increasingly emphasized in recent years. T. gondii has a high affinity for brain tissue where tachyzoites may form tissue cysts and persist for a life long time. Some psychiatric symptoms such as schizophrenia and mental retardation may be induced by the infection of T. gondii. Furthermore, experiments demonstrated that some antipsychotics and mood stabilizers used to treat psychosis displayed the function of inhibiting T. gondii replication. Investigations from various regions in China in psychotic patients support the hypotheses that psychosis may be linked to T. gondii infection.

PMID: 19467790 [PubMed - as supplied by publisher]

Tuesday, May 26, 2009

Forward genetics in Toxoplasma gondii reveals a family of rhoptry kinases that mediates pathogenesis

Eukaryot Cell. 2009 May 22. [Epub ahead of print]

Forward genetics in Toxoplasma gondii reveals a family of rhoptry kinases that mediates pathogenesis

Sibley LD, Qiu W, Fentress S, Taylor SJ, Khan A, Hui R.

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis,. MO 63130; Structural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.

Toxoplasma gondii is a widespread protozoan parasite that is both an important opportunistic pathogen and a model for related parasites in the phylum Apicomplexa. Toxoplasma offers a number of experimental advantages including convenient in vitro culture, small animal models, and forward and reverse genetic systems. Here we describe the development of forward genetic strategies to identify parasite genes that contribute to pathogenesis in laboratory mice. These studies led to the unexpected finding that a family of secretory serine/threonine kinases controls acute virulence in the mouse model. These S/T kinases are injected from secretory organelles in the parasite called the rhoptries, into the host cell during invasion. The rhoptry (ROP) protein family includes both pseudokinases and catalytically active kinases. Active ROPs are highly polymorphic, show dramatic differences in expression levels between strains, and are under strong selective pressure. Recent structural analysis indicates they also differ substantially from well-characterized kinases in animal cells. ROP kinases alter host cell gene transcription and set up an environment that favors parasite survival and replication, thus enhancing pathogenicity. The powerful combination of forward genetic screens and reverse genetic testing available in T. gondii will allow further characterization of these important virulence factors.

PMID: 19465561 [PubMed - as supplied by publisher]

The role of ATP-Binding Cassette (ABC) proteins in protozoan parasites

Mol Biochem Parasitol. 2009 May 20. [Epub ahead of print]

The role of ATP-Binding Cassette (ABC) proteins in protozoan parasites

Sauvage V, Aubert D, Escotte-Binet S, Villena I.

Laboratoire de Parasitologie-Mycologie, EA 3800, IFR 53, UFR Médecine, Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51095 Reims cedex, France.

The ATP-binding cassette (ABC) superfamily is one of the largest protein families with representatives in all kingdoms of life. Members of this superfamily are involved in a wide variety of transport processes with substrates ranging from small ions to relatively large polypeptides and polysaccharides, but also in cellular processes such as DNA repair, translation or regulation of gene expression. For many years, the role of ABC proteins was mainly investigated for their implication in drug resistance. However, recent studies focused rather on their physiological functions for the parasite. In this review, we present an overview of ABC proteins in major protozoan parasites including Leishmania, Trypanosoma, Plasmodium, Toxoplasma, Cryptosporidium and Entamoeba species. We will also discuss the role of characterized ABC transporters in the biology of the parasite and in drug resistance.

PMID: 19464325 [PubMed - as supplied by publisher]

A double-blind trial of adjunctive azithromycin in individuals with schizophrenia who are seropositive for Toxoplasma

Schizophr Res. 2009 May 22. [Epub ahead of print]

A double-blind trial of adjunctive azithromycin in individuals with schizophrenia who are seropositive for Toxoplasma gondii

Dickerson FB, Stallings CR, Boronow JJ, Origoni AE, Yolken RH.

Sheppard Pratt Health System, 6501 North Charles St., Baltimore, MD, 21204 USA.

Publication Types:
LETTER

PMID: 19464853 [PubMed - as supplied by publisher]

Evaluation of the Abbott ARCHITECT Toxo IgM assay

Diagn Microbiol Infect Dis. 2009 May 21. [Epub ahead of print]

Evaluation of the Abbott ARCHITECT Toxo IgM assay

Sickinger E, Braun HB, Praast G, Stieler M, Gundlach C, Birkenbach C, Prostko J, Palafox MA, Frias E, Hsu S, Matias M, Pucci D, Hausmann M, Sagel U, Smith D.

Abbott GmbH & Co. KG, Max-Planck-Ring 2, Wiesbaden-Delkenheim 65205, Germany.

Development of the ARCHITECT Toxo IgM assay has been done to assist the clinician in acute Toxoplasma gondii infection detection, especially in pregnant women. Its use, in conjunction with ARCHITECT Toxo IgG and Toxo Avidity assays, will provide an array of assays particularly useful in the monitoring of pregnant females to determine the risk of maternal transmission of the parasite. Specificity results from 2 testing sites, using populations of pregnant females, hospital patients, and blood donors, demonstrated that the assay has an overall resolved relative specificity of 99.89% (confidence interval, 99.68-99.98%). Relative specificity for pregnant female specimens was 99.95% (n = 2031). Excellent seroconversion sensitivity was observed for the ARCHITECT Toxo IgM assay, which was similar to the Abbott AxSYM Toxo IgM assay (Abbott Laboratories, Abbott Park, IL). In more than 90% of the panels tested, the 1st bleed detected in the serial bleeds was the same for both assays.

PMID: 19464840 [PubMed - as supplied by publisher]

Friday, May 22, 2009

Whole genome sequencing of a natural recombinant Toxoplasma gondii strain reveals chromosome sorting and local allelic variants

Genome Biol. 2009 May 20;10(5):R53. [Epub ahead of print]

Whole genome sequencing of a natural recombinant Toxoplasma gondii strain reveals chromosome sorting and local allelic variants

Lindstrom Bontell I, Hall N, Ashelford KE, Dubey JP, Boyle JP, Lindh J, Smith JE.

ABSTRACT: BACKGROUND: Toxoplasma gondii is a zoonotic parasite of global importance. In common with many protozoan parasites it has the capacity for sexual recombination, but current evidence suggests this is rarely employed. The global population structure is dominated by a small number of clonal genotypes, which exhibit biallelic variation and limited intralineage divergence. Little is known of the genotypes present in Africa despite the importance of AIDS associated toxoplasmosis. RESULTS: We here present extensive sequence analysis of eight isolates from Uganda, including the whole genome sequencing of a type II/III recombinant isolate, TgCkUg2. 454 sequencing gave 84% coverage across the approximate 61Mb genome and over 70,000 single nucleotide polymorphisms (SNPs) were mapped against reference strains. TgCkUg2 was shown to contain entire chromosomes of either type II or type III origin demonstrating chromosome sorting rather than intrachromosomal recombination. 1252 novel polymorphisms were mapped and clusters of new SNPs within coding sequence implied selective pressure on a number of genes, including surface antigens and rhoptry proteins. Further sequencing of the remaining isolates, six type II and one type III strain, confirmed the presence of novel SNPs, suggesting these are local allelic variants within Ugandan type II strains. In mice, the type III isolate had parasite burdens at least 30-fold higher than type II isolates, while the recombinant strain had an intermediate burden. CONCLUSIONS: Our data demonstrate that recombination between clonal lineages does occur in nature but there is nevertheless close homology between African and North American isolates. The quantity of high confidence SNP data generated in this study and the availability of the putative parental strains to this natural recombinant provide an excellent basis for future studies of the genetic divergence and of genotype-phenotype relationships.

PMID: 19457243 [PubMed - as supplied by publisher]

Wednesday, May 20, 2009

Sequential processing of the Toxoplasma apicoplast membrane protein FtsH1 in topologically distinct domains during intracellular trafficking

Mol Biochem Parasitol. 2009 Aug;166(2):126-33. Epub 2009 Mar 21

Sequential processing of the Toxoplasma apicoplast membrane protein FtsH1 in topologically distinct domains during intracellular trafficking

Karnataki A, Derocher AE, Feagin JE, Parsons M.

Seattle Biomedical Research Institute, 307 Westlake Ave. N., Seattle, WA 98109, USA; Interdisciplinary Program in Pathobiology, Department of Global Health, University of Washington, Seattle, WA 98195, United States.

FtsH proteins are hexameric transmembrane proteases found in chloroplasts, mitochondria and bacteria. In the protozoan Toxoplasma gondii, FtsH1 is localized to membranes of the apicoplast, a relict chloroplast present in many apicomplexan parasites. We have shown that although T. gondii FtsH1 lacks the typical bipartite targeting presequence seen on apicoplast luminal proteins, it is targeted to the apicoplast via the endoplasmic reticulum. In this report, we show that FtsH1 undergoes processing events to remove both the N- and C-termini, which are topologically separated by the membrane in which FtsH1 is embedded. Pulse-chase analysis showed that N-terminal cleavage precedes C-terminal cleavage. Unlike the processing of the N-terminal transit peptide of luminal proteins, which occurs in the apicoplast, analysis of ER-retained mutants showed that N-terminal processing of FtsH1 occurs in the endoplasmic reticulum. Two of four FtsH1 mutants bearing internal epitope tags accumulated in structures peripheral to the apicoplast, implying that FtsH1 trafficking is highly sensitive to changes in protein structure. These mutant proteins did not undergo C-terminal processing, suggesting that this processing step occurs after localization to the plastid. Mutation of the peptidase active site demonstrated that neither processing event occurs in cis. These data support a model in which multiple proteases act at different points of the trafficking pathway to form mature FtsH1, making its processing more complex than other FtsHs and unique among apicoplast proteins described thus far.

PMID: 19450729 [PubMed - in process]

Wednesday, May 13, 2009

Mem Inst Oswaldo Cruz - Special issue on Toxoplasma

Table of contentsMem. Inst. Oswaldo Cruz vol.104 no.2 Rio de Janeiro Mar. 2009
ForewordCupolillo, Elisa; Bahia-Oliveira, Lílian MG; Dardé, Marie-Laure
· text in english · pdf in english

Toxoplasma gondii centennial anniversary: 100 years of research to celebrate all over the worldBahia-Oliveira, Lílian MG; Dardé, Marie-Laure; Amendoeira, Maria Regina Reis
· text in english · pdf in english

Toxoplasma gondii: 1908-2008, homage to Nicolle, Manceaux and SplendoreFerguson, David J P
· abstract in english · text in english · pdf in english

Brazilian contribution for a better knowledge on the biology of Toxoplasma gondiiSouza, Wanderley de; DaMatta, Renato A; Attias, Márcia
· abstract in english · text in english · pdf in english

Understanding mechanisms and the role of differentiation in pathogenesis of Toxoplasma gondii: a reviewSullivan Jr, William J; Smith, Aaron T; Joyce, Bradley R
· abstract in english · text in english · pdf in english

Host genetic and epigenetic factors in toxoplasmosisJamieson, Sarra E; Cordell, Heather; Petersen, Eskild; McLeod, Rima; Gilbert, Ruth E; Blackwell, Jenefer M
· abstract in english · text in english · pdf in english

Interaction and cystogenesis of Toxoplasma gondii within skeletal muscle cells in vitroGuimarães, Erick Vaz; Carvalho, Laís de; Barbosa, Helene Santos
· abstract in english · text in english · pdf in english

Toxoplasma gondii infection induces lipid metabolism alterations in the murine hostMilovanović, Ivan; Vujanić, Marija; Klun, Ivana; Bobić, Branko; Nikolić, Aleksandra; Ivović, Vladimir; Trbovich, Alexander M; Djurković-Djaković, Olgica
· abstract in english · text in english · pdf in english

Expansion of host range as a driving force in the evolution of ToxoplasmaBoothroyd, John C
· abstract in english · text in english · pdf in english

What new cell biology findings could bring to therapeutics: is it time for a phenome-project in Toxoplasma gondii?Meissner, Markus; Klaus, Katrin
· abstract in english · text in english · pdf in english

Population biology of Toxoplasma gondii: what's out and where did they come fromDubey, JP; Su, Chunlei
· abstract in english · text in english · pdf in english

Spontaneous stage differentiation of mouse-virulent Toxoplasma gondii RH parasites in skeletal muscle cells: an ultrastructural evaluationFerreira-da-Silva, Marialice da Fonseca; Rodrigues, Renata Mendonça; Andrade, Elisabete Ferreira de; Carvalho, Laís de; Gross, Uwe; Lüder, Carsten G K; Barbosa, Helene Santos
· abstract in english · text in english · pdf in english

Advances in understanding immunity to Toxoplasma gondiiTait, Elia D; Hunter, Christopher A
· abstract in english · text in english · pdf in english

Immunopathology in ocular toxoplasmosis: facts and cluesGarweg, Justus G; Candolfi, Ermanno
· abstract in english · text in english · pdf in english

Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literatureSchreiner, Maximilian; Liesenfeld, Oliver
· abstract in english · text in english · pdf in english

Toxoplasma gondii and the Immunity-Related GTPase (IRG) resistance system in mice: a reviewZhao, Yang Oliver; Rohde, Christoph; Lilue, Jing Tao; Könen-Waisman, Stephanie; Khaminets, Aliaksandr; Hunn, Julia Petra; Howard, Jonathan Charles
· abstract in english · text in english · pdf in english

Experimental reinfection of BALB/c mice with different recombinant type I/III strains of Toxoplasma gondii: involvement of IFN-³ and IL-10Brandão, Geane Peroni; Melo, Maria Norma; Gazzinelli, Ricardo Tostes; Caetano, Braulia Costa; Ferreira, Adriana Melo; Silva, Letícia Azevedo; Vitor, Ricardo Wagner Almeida
· abstract in english · text in english · pdf in english

Veterinary vaccines against Toxoplasma gondiiInnes, Elisabeth A; Bartley, Paul M; Maley, Stephen; Katzer, Frank; Buxton, David
· abstract in english · text in english · pdf in english

Vaccines against Toxoplasma gondii: challenges and opportunitiesJongert, Erik; Roberts, Craig W; Gargano, Nicola; Förster-Wald, Elisabeth; Petersen, Eskild
· abstract in english · text in english · pdf in english

CD40, autophagy and Toxoplasma gondiiSubauste, Carlos S
· abstract in english · text in english · pdf in english

Host immune response to Toxoplasma gondii and Ascaris lumbricoides in a highly endemic area: evidence of parasite co-immunomodulation properties influencing the outcome of both infectionsBahia-Oliveira, Lílian MG; Silva, Juliana Azevedo da; Peixoto-Rangel, Alba Lucinia; Boechat, Marcela Santana Bastos; Oliveira, Annelise M Wilken Abreu; Massara, Cristiano L; Peixe, Ricardo Guerra
· abstract in english · text in english · pdf in english

Oocyst wall formation and composition in coccidian parasitesMai, Kelly; Sharman, Philippa A; Walker, Robert A; Katrib, Marilyn; Souza, David De; McConville, Malcolm J; Wallach, Michael G; Belli, Sabina I; Ferguson, David JP; Smith, Nicholas C
· abstract in english · text in english · pdf in english

Detection of Toxoplasma gondii oocysts in water: proposition of a strategy and evaluation in Champagne-Ardenne Region, FranceAubert, D; Villena, I
· abstract in english · text in english · pdf in english

The sero-prevalence of Toxoplasma gondii in British marine mammalsForman, Dan; West, Nathan; Francis, Janet; Guy, Edward
· abstract in english · text in english · pdf in english

Options for clinical trials of pre and post-natal treatments for congenital toxoplasmosisChêne, Geneviève; Thiébaut, Rodolphe
· abstract in english · text in english · pdf in english

Treatment for congenital toxoplasmosis: finding out what worksGilbert, Ruth
· abstract in english · text in english · pdf in english

Treating ocular toxoplasmosis: current evidenceStanford, MR; Gilbert, RE
· abstract in english · text in english · pdf in english

When are we going to celebrate the centenary of the discovery of efficient treatment for congenital toxoplasmosis?Peyron, F
· abstract in english · text in english · pdf in english

Why prevent, diagnose and treat congenital toxoplasmosis?McLeod, Rima; Kieffer, Francois; Sautter, Mari; Hosten, Tiffany; Pelloux, Herve
· abstract in english · text in english · pdf in english

Ocular toxoplasmosis: an update and review of the literatureCommodaro, Alessandra G; Belfort, Rubens N; Rizzo, Luiz Vicente; Muccioli, Cristina; Silveira, Claudio; Burnier Jr, Miguel N; Belfort Jr, Rubens
· abstract in english · text in english · pdf in english

Ocular toxoplasmosis: the influence of patient ageHolland, Gary N
· abstract in english · text in english · pdf in english

Contributions to the history of ocular toxoplasmosis in Southern BrazilMelamed, J
· abstract in english · text in english · pdf in english

Toxoplasma gondii in animals used for human consumptionTenter, Astrid M
· abstract in english · text in english · pdf in english

Congenital toxoplasmosis and DALYs in the NetherlandsKortbeek, LM; Hofhuis, A; Nijhuis, CDM; Havelaar, AH
· abstract in english · text in english · pdf in english

Prenatal screening for congenital toxoplasmosis in Campania: preliminary report on activities and resultsStagni, L; Romano, MA; Romano, A; Magli, A; Briganti, F; Del Pezzo, MA; Buffolano, W
· abstract in english · text in english · pdf in english

Factors associated with seropositivity for anti-Toxoplasma gondiiantibodies in pregnant women of Londrina, Paraná, BrazilLopes, FMR; Mitsuka-Breganó, R; Gonçalves, DD; Freire, RL; Karigyo, CJT; Wedy, GF; Matsuo, T; Reiche, EMV; Morimoto, HK; Capobiango, JD; Inoue, IT; Garcia, JL; Navarro, IT
· abstract in english · text in english · pdf in english

Prevalence of acute toxoplasmosis infection among 41,112 pregnant women and the mother-to-child transmission rate in a public hospital in South BrazilVarella, Ivana S; Canti, Ivete CT; Santos, Breno R; Coppini, Angela Z; Argondizzo, Luciana C; Tonin, Carina; Wagner, Mário B
· abstract in english · text in english · pdf in english

Diagnosis of congenital toxoplasmosis: prenatal and neonatal evaluation of methods used in Toulouse University Hospital and incidence of congenital toxoplasmosisBessières, MH; Berrebi, A; Cassaing, S; Fillaux, J; Cambus, JP; Berry, A; Assouline, C; Ayoubi, JM; Magnaval, JF
· abstract in english · text in english · pdf in english

Acute acquired toxoplasmosis: clinical-laboratorial aspects and ophthalmologic evaluation in a cohort of immunocompetent patientsNeves, ES; Bicudo, LN; Curi, AL; Carregal, E; Bueno, WF; Ferreira, RG; Amendoeira, MR; Benchimol, E; Fernandes, O
· abstract in english · text in english · pdf in english

Protective immunity against Toxoplasma challenge in mice by coadministration of T. gondii antigens and Eimeria profilin-like protein as an adjuvant

Vaccine. 2009 Apr 6;27(16):2274-81. Epub 2009 Jan 31

Protective immunity against Toxoplasma challenge in mice by coadministration of T. gondii antigens and Eimeria profilin-like protein as an adjuvant

Hedhli D, Dimier-Poisson I, Judge JW, Rosenberg B, Mévélec MN.

UMR 483 Université-INRA d'Immunologie Parasitaire, Vaccinologie et Biothérapie anti-infectieuse, IFR 136 Agents transmissibles et Infectiologie, UFR des Sciences Pharmaceutiques, Tours, France.

Toll-like receptor (TLR) ligands are attractive adjuvant candidates in vaccine development. Eimeria tenella profilin-like protein has recently been shown to be a potent agonist of the innate immune system through its recognition by Toll-like receptor-11. In this report, we studied the systemic and mucosal adjuvant activity of Eimeria profilin-like protein within a vaccinal strategy against Toxoplasma gondii in mice. Using intraperitoneal (i.p.) immunization, we observed that coadministration of the recombinant Eimeria antigen (rEA) with T. gondii antigen (TAg) effectively elevates plasma levels of IL-12p70 and consequently induced both enhanced specific humoral and Th1 cellular immune responses. The co-administration of TAg plus rEA by i.p route significantly enhanced the protection against T. gondii infection (62% brain cyst reduction) in comparison with control mice and with mice immunized with TAg alone (only 36% brain cyst reduction). After intranasal immunization, humoral and cellular responses were weak. However mice immunized nasally with TAg plus rEA were significantly protected with 50% of brain cyst reduction, conversely TAg immunized mice did not present any brain cyst reduction.These results indicate that Eimeria profilin-like protein would serve as an efficacious systemic and mucosal adjuvant inducing protective immune response against chronical stage of T. gondii infection through TLR11 activation.

PMID: 19428842 [PubMed - in process]

Protection in mice immunized with a heterologous prime-boost regime using DNA and recombinant pseudorabies expressing TgSAG1 against challenge

Vaccine. 2009 May 11;27(21):2741-5. Epub 2009 Mar 25

Protection in mice immunized with a heterologous prime-boost regime using DNA and recombinant pseudorabies expressing TgSAG1 against Toxoplasma gondii challenge

Shang L, Liu Q, Liu W, Men J, Gao S, Jiang L, Wang Z, Zhai Y, Jin H, Lian H, Chen C, Xia Z, Yuan Z, Zhu XQ.

Laboratory of Parasitology, Veterinary Institute, Academy of Military Medical Sciences, Changchun 130062, Jilin Province, China.

An effective vaccine of animals can block transmission of Toxoplasma gondii to humans. In this study, mice have been protected against lethal T. gondii challenge by a prime-boost vaccination strategy using DNA vaccine pVAX/TgSAG1 and recombinant pseudorabies virus rPRV/TgSAG1, both expressing the major immunodominant surface antigen of T. gondii (TgSAG1). High levels of splenocyte proliferative responses and significant levels of IFN-gamma resulted, with strong cytotoxic T lymphocyte (CTL) responses in vitro. After lethal challenge, prime-boost vaccinated mice showed an increased survival time (15.4+/-5.0 days) and a 40% survival rate compared with controls who all died within 11 days of challenge. Results of the present study indicated that this novel immunization strategy is useful in enhancing immune protection in mice against lethal T. gondii infection, which would provide foundation for the development of effective vaccines against T. gondii.

PMID: 19428887 [PubMed - in process]

Global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis

Int J Parasitol. 2009 May 8. [Epub ahead of print]

Toxoplasmosis snapshots: Global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis

Pappas G, Roussos N, Falagas ME.

Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; Institute of Continuing Medical Education of Ioannina, Greece.

Toxoplasma gondii's importance for humans refers mainly to primary infection during pregnancy, resulting in abortion/stillbirth or congenital toxoplasmosis. The authors sought to evaluate the current global status of T. gondii seroprevalence and its correlations with risk factors, environmental and socioeconomic parameters. Literature published during the last decade on toxoplasmosis seroprevalence, in women who were pregnant or of childbearing age, was retrieved. A total of 99 studies were eligible; a further 36 studies offered seroprevalence data from regions/countries for which no data on pregnancy/childbearing age were available. Foci of high prevalence exist in Latin America, parts of Eastern/Central Europe, the Middle East, parts of southeast Asia and Africa. Regional seroprevalence variations relate to individual subpopulations' religious and socioeconomic practices. A trend towards lower seroprevalence is observed in many European countries and the United States of America (USA). There is no obvious climate-related gradient, excluding North and Latin America. Immigration has affected local prevalence in certain countries. We further sought to recognize specific risk factors related to seropositivity; however, such risk factors are not reported systematically. Population awareness may affect recognition of said risks. Global toxoplasmosis seroprevalence is continuingly evolving, subject to regional socioeconomic parameters and population habits. Awareness of these seroprevalence trends, particularly in the case of women of childbearing age, may allow proper public health policies to be enforced, targeting in particular seronegative women of childbearing age in high seroprevalence areas.

PMID: 19433092 [PubMed - as supplied by publisher]

Friday, May 08, 2009

Induction and regulation of conoid extrusion in Toxoplasma gondii

Cell Microbiol. 2009 Mar 16. [Epub ahead of print]

Induction and regulation of conoid extrusion in Toxoplasma gondii

Del Carmen MG, Mondragón M, González S, Mondragón R.

Departamento de Bioquímica. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN). Avenida IPN N degrees 2508. Sn Pedro Zacatenco, Del. Gustavo A. Madero. México D. F. CP 07360, México.

Summary Cell invasion by the intracellular parasite Toxoplasma gondii occurs through an active process that involves dynamic events, such as gliding motility and conoid extrusion, followed by a sequential secretion from specialized secretory organelles. Increase of intracellular Ca(2+) by ionophores induces conoid extrusion, although in an irreversible way, thus limiting the characterization of the regulatory pathways. In this report we studied the effect of different activating conoid conditions to characterize the regulatory mechanisms involved. Exposure of tachyzoites to ethanol, a well-known activator of microneme secretion through the increase of intracellular Ca(2+), induced conoid extrusion without affecting parasite viability nor its in vitro invasive capability, in a process that could be completely reverted and repeatedly reactivated. A temporal relationship between conoid extrusion and microneme secretion was here studied. Under this condition, signal transduction pathways and the precise role of the parasite cytoskeleton were characterized. Our results indicate that phospholipase C, Ca(2+) released through channels sensitive to inositol-3-phosphate and ryanodine, as well as myosin together with actin filaments, but not microtubules, all participate in conoid extrusion. Specific inhibitors for serine-threonine kinases blocked conoid extrusion; in contrast, calmodulin inhibitors did not affect the induction. A regulatory model for conoid activation is here proposed.

PMID: 19416276 [PubMed - as supplied by publisher]

Changing climate-changing pathogens: Toxoplasma gondii in North-Western Europe

Parasitol Res. 2009 May 6. [Epub ahead of print]

Changing climate-changing pathogens: Toxoplasma gondii in North-Western Europe

Meerburg BG, Kijlstra A.

Wageningen University and Research Centre, Plant Research International, P.O. Box 616, 6700 AP, Wageningen, The Netherlands, Bastiaan.Meerburg@wur.nl.

In this review, we describe the effects of global climate change for one specific pathogen: the parasite Toxoplasma gondii. It is postulated that an increase of T. gondii prevalence in humans can occur in some regions of North-Western Europe as a result of changing environmental conditions. Such a change can be predicted by using Global Climate Change models. We have elaborated such a prediction for one scenario (SRES A1) by using one specific model (CCSR/NRIES) as an example. Next to environmental factors, also anthropogenic factors may contribute to increased prevalence of T. gondii in this region. In order to counter the potential severe consequences of a potential increase resulting from the combination of climatic and anthropogenic factors, there is an urgent need for the development of a human vaccine. Until a vaccine that offers complete protection is developed, the emphasis should be on treatment optimization and prevention.

PMID: 19418068 [PubMed - as supplied by publisher]

Over-expression of lactate dehydrogenase enhances differentiation under alkaline conditions

Exp Parasitol. 2009 Jun;122(2):155-61

Toxoplasma gondii: over-expression of lactate dehydrogenase enhances differentiation under alkaline conditions

Liwak U, Ananvoranich S.

Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, Ont. N9B 3P4, Canada.

Toxoplasma gondii, an intracellular parasite, has two distinctive growth stages, namely rapidly growing tachyzoites and slowly growing bradyzoites. Here we report a unique physiological function of the last committed glycolytic enzyme of T. gondii, lactate dehydrogenase (TgLDH), which is present in two isoforms and expressed in a stage-specific manner. TgLDH1 is present in tachyzoites while TgLDH2 is found in bradyzoites. Using clonal transgenic parasites over-expressing either TgLDH1 or TgLDH2, we showed that the enzymatic activity, growth, and virulence of tachyzoites were unaffected by the presence of the recombinant protein. Interestingly, under alkaline conditions the presence of the recombinant TgLDH proteins increased the differentiation, as detected by the formation of cyst structures in vitro, while green fluorescent protein did not. The differentiation enhancement of the recombinant TgLDH1 and TgLDH2 strongly suggests that TgLDH1 and TgLDH2 have an important physiological function, in addition to being glycolytic enzymes and differentiation markers

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

PMID: 19422070 [PubMed - in process]

Thursday, May 07, 2009

Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma

J Immunol. 2009 May 15;182(10):6379-93

Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii

Schaeffer M, Han SJ, Chtanova T, van Dooren GG, Herzmark P, Chen Y, Roysam B, Striepen B, Robey EA.

Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

The intracellular parasite Toxoplasma gondii can establish persistent infection in the brain of a mammalian host, a standoff that involves the active participation of host CD8 T cells to control infection. CD8 T cells generally protect against intracellular pathogens by local delivery of effector molecules upon recognition of specific pathogen Ags on invaded host cells. However, the interactions between CD8 T cells, T. gondii, and APCs in the brain have not yet been examined. In this study we have used a mouse infection model in conjunction with two-photon microscopy of living brain tissue and confocal microscopy of fixed brain sections to examine the interactions between CD8 T cells, parasites, and APCs from chronically infected mice. We found that Ag-specific CD8 T cells were recruited to the brains of infected mice and persisted there in the presence of ongoing Ag recognition. Cerebral CD8 T cells made transient contacts with granuloma-like structures containing parasites and with individual CD11b(+) APCs, including some that did not contain parasites. In contrast, T cells ignored intact Ag-bearing cysts and did not contact astrocytes or neurons, including neurons containing parasites or cysts. Our data represent the first direct observation of the dynamics of T cell-parasite interactions within living tissue and provide a new perspective for understanding immune responses to persistent pathogens in the brain.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

PMID: 19414791 [PubMed - in process]

Tuesday, May 05, 2009

Organelle division: dynamin-related proteins in apicomplexans

Curr Biol. 2009 Apr 28;19(8):R334-6

Organelle division: dynamin-related proteins in apicomplexans

Webster WA, McFadden GI.

Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Victoria, Australia.

Establishing an infection within a host requires efficient invasion and division. In the intracellular parasite Toxoplasma gondii, these functions are mediated by dynamin-related proteins with a unique evolutionary history.

PMID: 19409284 [PubMed - in process]

Friday, May 01, 2009

Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence

APMIS. 2009 May;117(5-6):458-76

Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence

Blader IJ, Saeij JP

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. iblader@ouhsc.edu

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.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

PMID: 19400868 [PubMed - in process]

Possible high frequency of mixed infection in feral cats ( Felis domesticus) from St Kitts, West Indies

Parasitology. 2009 May;136(6):589-94

Isolation and characterization of viable Toxoplasma gondii isolates revealed possible high frequency of mixed infection in feral cats ( Felis domesticus) from St Kitts, West Indies

Dubey JP, Moura L, Majumdar D, Sundar N, Velmurugan GV, Kwok OC, Kelly P, Krecek RC, Su C.

United States Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Animal Parasitic Diseases Laboratory, Beltsville, MD 20705-2350, USA. jitender.dubey@ars.usda.gov

Cats are essential in the epidemiology of Toxoplasma gondii because they are the only hosts that can excrete the environmentally resistant oocysts in nature. Samples of serum, feces, and tissues from feral cats from St Kitts, West Indies were examined for T. gondii infection. Antibodies to T. gondii were assayed by the modified agglutination test, and found in 71 of 96 (73.9%) of cats with titres of 1:10 in six, 1: 20 in six,1:40 in seven,1: 80 in three, 1: 160 in 10, 1:320 in 13, 1:640 in nine, and 1:1,280 or higher in 17. Tissues of 10 cats were bio-assayed in mice. Toxoplasma gondii was isolated from tissues of 7 cats; from hearts of 6, from tongue of 5, and brains of 3 cats. All 7 isolates were avirulent for mice. Toxoplasma gondii oocysts were not found in the feces of 51 cats. Genotyping of these 7 T. gondii isolates by 10 multi-locus PCR-RFLP markers, including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and an apicoplast marker, Apico, revealed 4 genotypes, including clonal Type II, Type III and 2 unique genotypes. Five of the 7 cats had infection with 2 genotypes, indicating high frequency of mixed infection in the cat population on the St Kitts island.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 19402949 [PubMed - in process]

The Toxoplasma gondii Plastid replication and Repair Enzyme Complex, PREX

Parasitology. 2009 Apr 30:1-9. [Epub ahead of print]

The Toxoplasma gondii Plastid replication and Repair Enzyme Complex, PREX

Mukhopadhyay A, Chen CY, Doerig C, Henriquez FL, Roberts CW, Barrett MP.

Institute of Biomedical and Life Sciences, Division of Infection and Immunity, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow G12 8TA, UK.

SUMMARYA plastid-like organelle, the apicoplast, is essential to the majority of medically and veterinary important apicomplexan protozoa including Toxoplasma gondii and Plasmodium. The apicoplast contains multiple copies of a 35 kb genome, the replication of which is dependent upon nuclear-encoded proteins that are imported into the organelle. In P. falciparum an unusual multi-functional gene, pfprex, was previously identified and inferred to encode a protein with DNA primase, DNA helicase and DNA polymerase activities. Herein, we report the presence of a prex orthologue in T. gondii. The protein is predicted to have a bi-partite apicoplast targeting sequence similar to that demonstrated on the PfPREX polypeptide, capable of delivering marker proteins to the apicoplast. Unlike the P. falciparum gene that is devoid of introns, the T. gondii prex gene carries 19 introns, which are spliced to produce a contiguous mRNA. Bacterial expression of the polymerase domain reveals the protein to be active. Consistent with the reported absence of a plastid in Cryptosporidium species, in silico analysis of their genomes failed to demonstrate an orthologue of prex. These studies indicate that prex is conserved across the plastid-bearing apicomplexans and may play an important role in the replication of the plastid genome.

PMID: 19402939 [PubMed - as supplied by publisher]