Saturday, August 27, 2011

CD8α(+) Dendritic Cells Are the Critical Source of Interleukin-12 that Controls Acute Infection by Toxoplasma gondii Tachyzoites

Immunity. 2011 Aug 26;35(2):249-259

CD8α(+) Dendritic Cells Are the Critical Source of Interleukin-12 that Controls Acute Infection by Toxoplasma gondii Tachyzoites

Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A, Goldszmid RS, Sher A, Ploegh HL, Murphy TL, Sibley LD, Murphy KM

SourceDepartment of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.

Abstract
CD8α(+) dendritic cells (DCs) are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, secretion of interleukin-12 (IL-12) by CD8α(+) DCs suggests a role for these cells in response to Toxoplasma gondii antigens, although it remains unclear whether these cells are required for protection against T. gondii infection. Toward this goal, we examined T. gondii infection of Batf3(-/-) mice, which selectively lack only lymphoid-resident CD8α(+) DCs and related peripheral CD103(+) DCs. Batf3(-/-) mice were extremely susceptible to T. gondii infection, with decreased production of IL-12 and interferon-γ. IL-12 administration restored resistance in Batf3(-/-) mice, and mice in which IL-12 production was ablated only from CD8α(+) DCs failed to control infection. These results reveal that the function of CD8α(+) DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during T. gondii infection.

Copyright © 2011 Elsevier Inc. All rights reserved.

Intracellular Pathogens and CD8(+) Dendritic Cells: Dangerous Liaisons

Immunity. 2011 Aug 26;35(2):153-155

Intracellular Pathogens and CD8(+) Dendritic Cells: Dangerous Liaisons

Reizis B

SourceDepartment of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.

Abstract
CD8(+) dendritic cells comprise a distinct cell type whose function is unclear. In this issue of Immunity, Mashayekhi et al. (2011) show these cells are essential for protection against the parasite Toxoplasma, but Edelson et al. (2011) show they are hijacked by Listeria during initial spreading.

Copyright © 2011 Elsevier Inc. All rights reserved.

Antiphospholipid Syndrome following Toxoplasma Retinochoroiditis

Ocul Immunol Inflamm. 2011 Aug 24. [Epub ahead of print]

Antiphospholipid Syndrome following Toxoplasma Retinochoroiditis

Tavakoli M, Roghaee S, Soheilian R, Soheilian M

SourceOphthalmology Department and Ophthalmic Research Center, Labbafinejad Medical Center, Shahid Beheshti Medical University , Tehran , Iran.

Abstract
Purpose: To report a case of antiphospholipid syndrome (APS) following toxoplasma retinochoroiditis. Design: Interventional case report. Method: The patient was a 24-year-old female with an attack of visual loss due to toxoplasma retinochoroiditis concomitant with branch retinal vein occlusion. Retinitis resolved with anti-toxoplasma treatment. However, a recurrent episode of BRVO and vitreous hemorrhage occurred later. Result: In systemic evaluation, evidence of APS was detected, including high titers of anti-cardiolipin antibody, increased beta-2 microglobulin and anti-toxoplasma IgG antibody, and also low titers of C3, C4, and CH50. Conclusion: Ocular toxoplasmosis should be included in the list of etiologies of secondary APS. Systemic evaluation for detection of APS is a necessary approach to patients with toxoplasma retinochoroiditis and concomitant vascular accident.

PMID:21864013[PubMed - as supplied by publisher]

Tuesday, August 23, 2011

Two internal type II NADH dehydrogenases of Toxoplasma gondii are both required for optimal tachyzoite growth

Mol Microbiol. 2011 Aug 19. doi: 10.1111/j.1365-2958.2011.07807.x. [Epub ahead of print]

Two internal type II NADH dehydrogenases of Toxoplasma gondii are both required for optimal tachyzoite growth

Lin SS, Gross U, Bohne W

SourceInstitute of Medical Microbiology, University Medical Center Göttingen, Kreuzbergring 57, Göttingen D-37075, Germany.

Abstract
In many apicomplexan parasites the entry of electrons from NADH into the electron transport chain is governed by type II NADH dehydrogenases (NDH2s) instead of a canonical complex I. Toxoplasma gondii expresses two NDH2 isoforms, TgNDH2-I and TgNDH2-II with no indication for stage-specific regulation. We dissected the orientation of both isoforms by using a split GFP assay and a protease protection assay after selective membrane permeabilization. The two approaches revealed that both TgNDH2 isoforms are internal enzymes facing with their active sites to the mitochondrial matrix. Single knock-out mutants displayed a decreased replication rate and a reduced mitochondrial membrane potential, which were both more severe in the Tgndh2-II-deleted than in the Tgndh2-I-deleted mutant. Complementation with a myc-tagged, ectopic copy of the deleted gene restored the growth rate and the mitochondrial membrane potential. However, an over-expression of the remaining intact isoform could not restore the phenotype, suggesting that the two TgNDH2 isoforms are non-redundant and possess functional differences. Together, our studies indicate that although TgNDH2-I and TgNDH2-II are individually non-essential, the expression of both internal isoforms is required to maintain the mitochondrial physiology in T. gondii tachyzoites.

© 2011 Blackwell Publishing Ltd.

PMID:21854467[PubMed - as supplied by publisher]

Predator Cat Odors Activate Sexual Arousal Pathways in Brains of Toxoplasma gondii Infected Rats

PLoS One. 2011;6(8):e23277. Epub 2011 Aug 17

Predator Cat Odors Activate Sexual Arousal Pathways in Brains of Toxoplasma gondii Infected Rats

House PK, Vyas A, Sapolsky R

SourceProgram in Neuroscience, Stanford University, Stanford, California, United States of America.

Abstract
Cat odors induce rapid, innate and stereotyped defensive behaviors in rats at first exposure, a presumed response to the evolutionary pressures of predation. Bizarrely, rats infected with the brain parasite Toxoplasma gondii approach the cat odors they typically avoid. Since the protozoan Toxoplasma requires the cat to sexually reproduce, this change in host behavior is thought to be a remarkable example of a parasite manipulating a mammalian host for its own benefit. Toxoplasma does not influence host response to non-feline predator odor nor does it alter behavior on olfactory, social, fear or anxiety tests, arguing for specific manipulation in the processing of cat odor. We report that Toxoplasma infection alters neural activity in limbic brain areas necessary for innate defensive behavior in response to cat odor. Moreover, Toxoplasma increases activity in nearby limbic regions of sexual attraction when the rat is exposed to cat urine, compelling evidence that Toxoplasma overwhelms the innate fear response by causing, in its stead, a type of sexual attraction to the normally aversive cat odor.

PMID:21858053[PubMed - in process]

Saturday, August 20, 2011

Protection in a hamster model of congenital toxoplasmosis

Vet Parasitol. 2011 Aug 2. [Epub ahead of print]

Protection in a hamster model of congenital toxoplasmosis

Freyre A, Araujo FA, Fialho CG, Bigatti LE, Falcón JD

SourceLaboratorio de Toxoplasmosis, Departamento de Parasitología, Facultad de Veterinaria, Montevideo, Uruguay.

Abstract
Almost uniform protection against congenital toxoplasmosis initiated by inoculations with cysts and oocysts of the parasite was seen in the hamster model, among strains of different genotypes. Because the RH immunization prior to pregnancy has to be controlled with medication for most of the hamsters to survive, and also some congenital transmission of Toxoplasma was observed during the chronic stage of the infection, the hamster is considered less practical than the rat and the BALB/c mouse models. It is concluded that the hamster model closely resembles protection against congenital infection in nature, where most of the pregnant women and ewes that experienced a toxoplasma infection previously, protect their fetuses against an infection with the parasite during pregnancy.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID:21846582[PubMed - as supplied by publisher]

Parasiticidal activity of Haemaphysalis longicornis longicin P4 peptide against Toxoplasma gondii

Peptides. 2011 Aug 9. [Epub ahead of print]

Parasiticidal activity of Haemaphysalis longicornis longicin P4 peptide against Toxoplasma gondii

Tanaka T, Maeda H, Matsuo T, Boldbattar D, Umemiya-Shirafuji R, Kume A, Suzuki H, Xuan X, Tsuji N, Fujisaki K

SourceLaboratory of Emerging Infectious Diseases, Department of Frontier Veterinary Science, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.

Abstract
The Haemaphysalis longicornis longicin P4 peptide is an active part peptide produced by longicin which displays bactericidal activity against both Gram-negative and Gram-positive bacteria and other microorganisms. In the present study, the effect of the longicin P4 peptide on the infectivity of Toxoplasma gondii parasites was examined in vitro. Tachyzoites of T. gondii incubated with longicin P4 had induced aggregation and lost the trypan blue dye exclusion activity and the invasion ability into the mouse embryonal cell line (NIH/3T3). Longicin P4 was located at the surface of T. gondii tachyzoites, as demonstrated by fluoresce microscopic analysis. An electron microscopic analysis and a fluorescence propidium iodide exclusion assay of tachyzoites exposed to longicin P4 revealed pore formation in the cellular membrane, membrane disorganization, and hollowing as well as cytoplasmic vacuolization. The number of tachyzoites proliferated in mouse macrophage cell line (J774A.1) was significantly decreased by incubation with longicin P4. These findings suggested that longicin P4 conceivably impaired parasite membranes, leading to the destruction of Toxoplasma parasites in J774A.1 cells. Thus, longicin P4 is an interesting candidate for antitoxoplasmosis drug design that causes severe toxicity to T. gondii and plays an important role in reducing cellular infection. This is the first report showing that longicin P4 causes aggregation and membrane injury of parasites, leading to Toxoplasma tachyzoite destruction.

Copyright © 2011. Published by Elsevier Inc.

PMID:21849158[PubMed - as supplied by publisher]

RNA granules present only in extracellular Toxoplasma gondii increase parasite viability

Int J Biol Sci. 2011;7(7):960-7. Epub 2011 Aug 7

RNA granules present only in extracellular Toxoplasma gondii increase parasite viability

Lirussi D, Matrajt M

SourceDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.

Abstract
Toxoplasma gondii is an obligate intracellular parasite. When searching for a new cell to invade, the parasites have to confront the stress of being exposed to the extracellular environment. The mechanisms by which T. gondii survives outside the host cells are poorly understood. In this work we show that extracellular parasites form mRNA aggregates with characteristics of stress granules. Intracellular tachyzoites or bradyzoites do not form mRNA granules. We tested different stimuli that trigger granule formation in vitro and discovered that a buffer that mimics the host cell cytosol ionic composition (high potassium) strongly induces granule formation, suggesting that the granules arise when the parasites come in contact with the host cell cytosol during egress. We examined the importance of granule formation for parasite viability and show that the parasite populations that are able to form granules have a growth advantage, increased invasion, and decreased apoptosis in the extracellular environment. Overall, granule formation improves the fitness of extracellular parasites and increases the efficiency of the lytic cycle.

PMID:21850205[PubMed - in process]

Saturday, August 13, 2011

A Fine Balance between Life and Death: Modulation of BCL-2 Family Members by Toxoplasma gondii

Front Microbiol. 2011;2:39. Epub 2011 Mar 7

A Fine Balance between Life and Death: Modulation of BCL-2 Family Members by Toxoplasma gondii

Arrizabalaga G

SourceDepartment of Biological Sciences, University of Idaho Moscow, ID, USA.

PMID:21833301[PubMed - in process]

Overexpression of a cytosolic pyrophosphatase (TgPPase) reveals a regulatory role of pyrophosphate in glycolysis for Toxoplasma gondii

Biochem J. 2011 Aug 10. [Epub ahead of print]

Overexpression of a cytosolic pyrophosphatase (TgPPase) reveals a regulatory role of pyrophosphate in glycolysis for Toxoplasma gondii

Pace DA, Fang J, Cintrón R, Docampo MD, Moreno SN

Abstract
Pyrophosphate (PPi) is a critical element of cellular metabolism as both an energy donor and as an allosteric regulator of several metabolic pathways. The apicomplexan parasite, Toxoplasma gondii, uses PPi in place of ATP as an energy donor in at least two reactions: the glycolytic PPi-dependent phosphofructokinase (PFK), and the proton translocating vacuolar pyrophosphatase (V-H+-PPase). In the present work, we report the cloning, expression, and characterization of a cytosolic pyrophosphatase from T. gondii (TgPPase). Amino acid sequence alignment and phylogenetic analysis indicates that the gene encodes a family I soluble PPase. Overexpression of the enzyme in extracellular tachyzoites led to a 6-fold decrease in the cytosolic concentration of PPi relative to RH wild type tachyzoites. Unexpectedly, this subsequent reduction in pyrophosphate was associated with a higher glycolytic flux in the overexpressing mutants as evidenced by higher rates of proton and lactate extrusion. In addition to elevated glycolytic flux, TgPPase overexpressing tachyzoites also possessed higher ATP concentrations relative to wild type, RH parasites. These results implicate PPi as having a significant regulatory role in glycolysis and potentially other downstream processes that regulate growth and cell division.

PMID:21831041[PubMed - as supplied by publisher]

Thursday, August 11, 2011

Subcellular Antigen Location Influences T-Cell Activation during Acute Infection with Toxoplasma gondii

PLoS One. 2011;6(7):e22936. Epub 2011 Jul 28

Subcellular Antigen Location Influences T-Cell Activation during Acute Infection with Toxoplasma gondii

Gregg B, Dzierszinski F, Tait E, Jordan KA, Hunter CA, Roos DS

SourceDepartment of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Abstract
Effective control of the intracellular protozoan parasite Toxoplasma gondii depends on the activation of antigen-specific CD8(+) T-cells that manage acute disease and prevent recrudescence during chronic infection. T-cell activation in turn, requires presentation of parasite antigens by MHC-I molecules on the surface of antigen presenting cells. CD8(+) T-cell epitopes have been defined for several T. gondii proteins, but it is unclear how these antigens enter into the presentation pathway. We have exploited the well-characterized model antigen ovalbumin (OVA) to investigate the ability of parasite proteins to enter the MHC-I presentation pathway, by engineering recombinant expression in various organelles. CD8(+) T-cell activation was assayed using 'B3Z' reporter cells in vitro, or adoptively-transferred OVA-specific 'OT-I' CD8(+) T-cells in vivo. As expected, OVA secreted into the parasitophorous vacuole strongly stimulated antigen-presenting cells. Lower levels of activation were observed using glycophosphatidyl inositol (GPI) anchored OVA associated with (or shed from) the parasite surface. Little CD8(+) T-cell activation was detected using parasites expressing intracellular OVA in the cytosol, mitochondrion, or inner membrane complex (IMC). These results indicate that effective presentation of parasite proteins to CD8(+) T-cells is a consequence of active protein secretion by T. gondii and escape from the parasitophorous vacuole, rather than degradation of phagocytosed parasites or parasite products.

PMID:21829561[PubMed - in process]

Wednesday, August 10, 2011

Solution structure and dynamics of ADF from Toxoplasma gondii

J Struct Biol. 2011 Jul 26. [Epub ahead of print]

Solution structure and dynamics of ADF from Toxoplasma gondii

Yadav R, Pathak PP, Shukla V, Jain A, Srivastava S, Tripathi S, Krishna Pulavarti SV, Mehta S, David Sibley L, Arora A

SourceMolecular and Structural Biology Division, Central Drug Research Institute, Lucknow 226 001, India.

Abstract
Toxoplasma gondii (TgADF) belongs to a functional subtype characterized by strong G-actin sequestering activity and low F-actin severing activity. Among the characterized ADF/cofilin proteins, TgADF has the shortest length and is missing a C-terminal helix implicated in F-actin binding. In order to understand its characteristic properties, we have determined the solution structure of TgADF and studied its backbone dynamics from (15)N-relaxation measurements. TgADF has conserved ADF/cofilin fold consisting of a central mixed β-sheet comprised of six β-strands that are partially surrounded by three α-helices and a C-terminal helical turn. The high G-actin sequestering activity of TgADF relies on highly structurally and dynamically optimized interactions between G-actin with the G-actin binding surface of TgADF. The equilibrium dissociation constant for TgADF and rabbit muscle G-actin was 23.81nM, as measured by ITC, which reflects very strong affinity of TgADF and G-actin interactions. The F-actin binding site of TgADF is partially formed, with a shortened F-loop that does not project out of the ellipsoid structure and a C-terminal helical turn in place of the C-terminal helix α4. Yet, it is more rigid than the typical F-actin binding site of Leishmania donovani cofilin. Experimental observations and structural features do not support the interaction of PIP2 with TgADF, and PIP2 does not affect the interaction of TgADF with G-actin. Overall, this study suggests that conformational flexibility of G-actin binding sites enhances the affinity of TgADF for G-actin, while conformational rigidity of F-actin binding sites of conventional ADF/cofilins is necessary for stable binding to F-actin.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:21820516[PubMed - as supplied by publisher]

Population genetics of Toxoplasma gondii: New perspectives from parasite genotypes in wildlife

Vet Parasitol. 2011 Jul 20. [Epub ahead of print]

Population genetics of Toxoplasma gondii: New perspectives from parasite genotypes in wildlife

Wendte JM, Gibson AK, Grigg ME

SourceMolecular Parasitology Unit, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA; Department of Veterinary Pathobiology, Oklahoma State University Center for Veterinary Health Sciences, Stillwater, OK 74074, USA.

Abstract
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.

Published by Elsevier B.V.

PMID:21824730[PubMed - as supplied by publisher]

Saturday, August 06, 2011

Changes in Toxoplasma Diagnosis

J Med Microbiol. 2011 Aug 4. [Epub ahead of print]

Changes in Toxoplasma Diagnosis

Chatterton JM, McDonagh S, Spence N, Ho-Yen DO.
SourceScottish Toxoplasma Reference Laboratory.

Abstract
The serological laboratory workload in detecting toxoplasma infection may be expected to change with changes in the clinical profile of patient populations. We have examined the clinical information and laboratory results for patients referred to the Scottish Toxoplasma Reference Laboratory in April to March 1999/2000 and 2009/2010. Numbers of patient sera submitted for testing were similar (1624 and 1552) but there was a change in the clinical profile with a significant fall in patients with symptoms of current infection (612 versus 335; p < 0.0001) and a significant rise in immunocompromised patients (275 versus 531; p = 0.0001). Although the percentage of patient samples with toxoplasma antibody decreased (53.9% versus 35.5%; p < 0.0001) the number of positives increased with age demonstrating the continuing risk of toxoplasma infection. More cases of current infection were identified in 2009/10 than in 1999/2000 (48 versus 35). This increase was significant both for all females with current infection (p = 0.0253) and also for those in the childbearing 20-39 age group (p = 0.0388). Our literature search did not find any published information on toxoplasma workload in the last decade. In summary, we have shown that there have been significant changes in the laboratory diagnosis of toxoplasma infection but it is as important as ever that effective diagnostic strategies are maintained.

PMID:21816946[PubMed - as supplied by publisher]

Wednesday, August 03, 2011

Ribonucleotide Reductase as a Target to Control Apicomplexan Diseases

Curr Issues Mol Biol. 2011 Jul 26;14(1):9-26. [Epub ahead of print]

Ribonucleotide Reductase as a Target to Control Apicomplexan Diseases

Munro JB, Silva JC

SourceDepartment of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract
Malaria is caused by species in the apicomplexan genus Plasmodium, which infect hundreds of millions of people each year and kill close to one million. While malaria is the most notorious of the apicomplexan-caused diseases, other members of eukaryotic phylum Apicomplexa are responsible for additional, albeit less well-known, diseases in humans, economically important livestock, and a variety of other vertebrates. Diseases such as babesiosis (hemolytic anemia), theileriosis and East Coast Fever, cryptosporidiosis, and toxoplasmosis are caused by the apicomplexans Babesia, Theileria, Cryptosporidium and Toxoplasma, respectively. In addition to the loss of human life, these diseases are responsible for losses of billions of dollars annually. Hence, the research into new drug targets remains a high priority. Ribonucleotide reductase (RNR) is an essential enzyme found in all domains of life. It is the only means by which de novo synthesis of deoxyribonucleotides occurs, without which DNA replication and repair cannot proceed. RNR has long been the target of antiviral, antibacterial and anti-cancer therapeutics. Herein, we review the chemotherapeutic methods used to inhibit RNR, with particular emphasis on the role of RNR inhibition in Apicomplexa, and in light of the novel RNR R2_e2 subunit recently identified in apicomplexan parasites.

PMID:21791713[PubMed - as supplied by publisher]

Identification of Toxoplasma gondii cAMP Dependent Protein Kinase and Its Role in the Tachyzoite Growth

PLoS One. 2011;6(7):e22492. Epub 2011 Jul 20

Identification of Toxoplasma gondii cAMP Dependent Protein Kinase and Its Role in the Tachyzoite Growth

Kurokawa H, Kato K, Iwanaga T, Sugi T, Sudo A, Kobayashi K, Gong H, Takemae H, Recuenco FC, Horimoto T, Akashi H

SourceDepartment of Veterinary Microbiology, Faculty of Agriculture, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Abstract
BACKGROUND: cAMP-dependent protein kinase (PKA) has been implicated in the asexual stage of the Toxoplasma gondii life cycle through assaying the effect of a PKA-specific inhibitor on its growth rate. Since inhibition of the host cell PKA cannot be ruled out, a more precise evaluation of the role of PKA, as well as characterization of the kinase itself, is necessary.

METHODOLOGY/PRINCIPAL FINDING: The inhibitory effects of two PKA inhibitors, H89, an ATP-competitive chemical inhibitor, and PKI, a substrate-competitive mammalian natural peptide inhibitor, were estimated. In the in vitro kinase assay, the inhibitory effect of PKI on a recombinant T. gondii PKA catalytic subunit (TgPKA-C) was weaker compared to that on mammalian PKA-C. In a tachyzoite growth assay, PKI had little effect on the growth of tachyzoites, whereas H89 strongly inhibited it. Moreover, T. gondii PKA regulatory subunit (TgPKA-R)-overexpressing tachyzoites showed a significant growth defect.

CONCLUSIONS/SIGNIFICANCE: Our data suggest that PKA plays an important role in the growth of tachyzoites, and the inhibitory effect of substrate-competitive inhibitor PKI on T. gondii PKA was low compared to that of the ATP competitive inhibitor H89.

PMID:21799871[PubMed - in process] PMCID: PMC3140512

Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

Biol Lett. 2011 Jul 27. [Epub ahead of print]

Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

Thomas F, Lafferty KD, Brodeur J, Elguero E, Gauthier-Clerc M, Missé D

SourceIRD, MIVEGEC (UMR CNRS/IRD/UM1), 911 Ave. Agropolis, BP 64501, FR-34394 Montpellier cedex 5, France.

Abstract
We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations. Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4-67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

PMID:21795265[PubMed - as supplied by publisher]

Enforcing host cell polarity: an apicomplexan parasite strategy towards dissemination

Curr Opin Microbiol. 2011 Jul 25. [Epub ahead of print]

Enforcing host cell polarity: an apicomplexan parasite strategy towards dissemination

Baumgartner M

SourceUniversity of Bern, Vetsuisse Faculty, Molecular Pathobiology, Länggassstrasse 122, CH-3012 Bern, Switzerland.

Abstract
The propagation of apicomplexan parasites through transmitting vectors is dependent on effective dissemination of parasites inside the mammalian host. Intracellular Toxoplasma and Theileria parasites face the challenge that their spread inside the host depends in part on the motile capacities of their host cells. In response, these parasites influence the efficiency of dissemination by altering adhesive and/or motile properties of their host cells. Theileria parasites do so by targeting signalling pathways that control host cell actin dynamics. The resulting enforced polar host cell morphology facilitates motility and invasiveness, by establishing focal adhesion and invasion structures at the leading edge of the infected cell. This parasite strategy highlights mechanisms of motility regulation that are also likely relevant for immune or cancer cell motility.