scholarly journals Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain

2009 ◽  
Vol 77 (12) ◽  
pp. 5380-5388 ◽  
Author(s):  
Jason P. Gigley ◽  
Barbara A. Fox ◽  
David J. Bzik
Keyword(s):  
Toxoplasma Gondii ◽  
Vaccine Strain ◽  
Chronic Infection ◽  
Toxoplasmic Encephalitis ◽  
Type I ◽  
Type Ii ◽  
Chronic Type ◽  
Toxoplasma Gondii Infection ◽  
Brain Cysts

ABSTRACT C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8+ immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain.

scholarly journals Role of Cytokines and Major Histocompatibility Complex Restriction in Mouse Resistance to Infection with a Natural Recombinant Strain (Type I-III) of Toxoplasma gondii

2003 ◽  
Vol 71 (11) ◽  
pp. 6392-6401 ◽  
Author(s):  
Blima Fux ◽  
Cibele V. Rodrigues ◽  
Ricardo W. Portela ◽  
Neide M. Silva ◽  
Chunlei Su ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Toxoplasma Gondii ◽  
Genetic Markers ◽  
Recombinant Strain ◽  
Cyst Formation ◽  
Toxoplasmic Encephalitis ◽  
Type I ◽  
Type Ii ◽  
Histocompatibility Complex ◽  
Mhc Haplotype

ABSTRACT Herein we characterized various genetic markers and the biological behavior of a natural recombinant strain of Toxoplasma gondii (P-Br). From nine genetic markers analyzed, three (B1, ROP1, and SAG1) and three (cS10-A6, GRA6, and SAG3) markers belong to parasites from the type I and type III lineages, respectively. The SAG2 and L363 loci were shown to be type I-III chimera alleles. The cB2l-4 microsatellite marker showed a unique haplotype. The P-Br strain presented low virulence in the acute phase of infection and was cystogenic during the chronic infection. The interleukin 12/gamma interferon axis and inducible nitric oxide synthase were main determinants of resistance during the acute infection with the P-Br strain. As opposed to infection with the type II strain of T. gondii (ME-49), peroral infection with the P-Br strain led only to a light inflammatory infiltrate and no major lesions in the intestine of the C57BL/6 mice. In addition, the BALB/c (resistant to ME-49) and C57BL/6 (susceptible to ME-49) mice were shown, respectively, to be more susceptible and more resistant to cyst formation and toxoplasmic encephalitis when infected with the P-Br strain. Further, the C57BL/KsJ and DBA2/J congenic strains containing major histocompatibility complex (MHC) haplotype “d” were more resistant than the parental strains (C57BL/6 and DBA1/J), when infected with the ME-49 but not with the P-Br strain. Together, our results indicate that resistance to cyst formation and toxoplasmic encephalitis induced during infection with P-Br is not primarily controlled by the MHC haplotype d, as previously reported for type II strains of T. gondii.

scholarly journals Nonreplicating, Cyst-Defective Type II Toxoplasma gondii Vaccine Strains Stimulate Protective Immunity against Acute and Chronic Infection

2015 ◽  
Vol 83 (5) ◽  
pp. 2148-2155 ◽  
Author(s):  
Barbara A. Fox ◽  
David J. Bzik
Keyword(s):  
Toxoplasma Gondii ◽  
Chronic Infection ◽  
Acute Infection ◽  
Cyst Formation ◽  
Type I ◽  
Type Ii ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Monophosphate Decarboxylase ◽  
Uracil Auxotroph

Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection byToxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion ofOMPDCinduced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δku80Δompdcmutants stimulated a fully protective CD8+T cell-dependent immunity that prevented acute infection by type I and type II strains ofT. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming Δompdcmutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine.

scholarly journals Immunization with plasmid DNA expressing Heat Shock Protein 40 confers prophylactic protection against chronic Toxoplasma gondii infection in Kunming mice

Parasite ◽  
2018 ◽  
Vol 25 ◽  
pp. 37
Author(s):  
Zhong-Yuan Li ◽  
Jing Lu ◽  
Nian-Zhang Zhang ◽  
Hany M. Elsheikha ◽  
Jun-Ling Hou ◽  
...  
Keyword(s):  
Heat Shock ◽  
Toxoplasma Gondii ◽  
Heat Shock Protein ◽  
Control Mouse ◽  
Effective Vaccine ◽  
Type I ◽  
Immunogenic Proteins ◽  
Toxoplasma Gondii Infection ◽  
Brain Cysts ◽  
And Control

Toxoplasma gondii causes one of the most common protozoal diseases of humans and animals worldwide. With the aim of designing an effective vaccine against T. gondii infection, we examined the immunogenicity of a DNA vaccine expressing heat shock protein 40 (HSP40) against challenge with T. gondii (type I RH and type II Pru) strains in Kunming mice. The plasmid pVAX1-HSP40 was constructed and used to immunize mice by intramuscular injection for three sequential immunizations with two-week intervals. This immunization regimen significantly reduced parasite cyst burden in pVAX1-HSP40-immunized mice (1871.9 ± 142.3) compared with control mouse groups immunized with pVAX1 (3479.2 ± 204.4), phosphate buffered saline (3024.4 ± 212.8), or left untreated (3275.0 ± 179.8) as healthy controls (p < 0.01). However, immunization failed to protect mice against challenge with the virulent RH strain. There was a significant increase in T lymphocyte subclasses (CD3e+CD4+ T and CD3e+CD8a+ T lymphocytes) in splenic tissues in immunized mice compared with controls (p < 0.05). However, the level of antibodies, lymphocyte proliferation and concentration of cytokines (IFN-γ, IL-2, IL-4, IL-10 and IL-12p70) were not significantly different between immunized and control mouse groups (p < 0.05). These data indicate that pVAX1-HSP40 induced specific immune responses and achieved a significant reduction in the number of brain cysts in Pru-infected mice, and thus can be tested in future immunization studies along with plasmids containing other immunogenic proteins as a cocktail vaccine to fully abolish chronic toxoplasmosis.

scholarly journals Minimal Invasive Surgery for Gastroesophageal Reflux Disease and Hiatus Hernia—Our Experience: A Case Series with Review of Literature

2021 ◽  
Author(s):  
Rafique Umer Harvitkar ◽  
Abhijit Joshi
Keyword(s):  
Retrospective Study ◽  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
Operating Time ◽  
Type I ◽  
Type Ii ◽  
The Mean ◽  
Gerd Symptoms

Abstract Introduction Laparoscopic fundoplication (LF) has almost completely replaced the open procedure performed for gastroesophageal reflux disease (GERD) and hiatus hernia (HH). Several studies have suggested that long-term results with surgery for GERD are better than a medical line of management. In this retrospective study, we outline our experience with LF over 10 years. Also, we analyze the factors that would help us in better patient selection, thereby positively affecting the outcomes of surgery. Patients and Methods In this retrospective study, we identified 27 patients (14 females and 13 males) operated upon by a single surgeon from 2010 to 2020 at our institution. Out of these, 25 patients (12 females and 13 males) had GERD with type I HH and 2 (both females) had type II HH without GERD. The age range was 24 to 75 years. All patients had undergone oesophago-gastro-duodenoscopy (OGD scopy). A total of 25 patients had various degrees of esophagitis. Two patients had no esophagitis. These patients were analyzed for age, sex, symptoms, preoperative evaluation, exact procedure performed (Nissen’s vs. Toupet’s vs. cruroplasty + gastropexy), morbidity/mortality, and functional outcomes. They were also reviewed to examine the length of stay, length of procedure, complications, and recurrent symptoms on follow-up. Symptoms were assessed objectively with a score for six classical GERD symptoms preoperatively and on follow-up at 1-, 4- and 6-weeks postsurgery. Further evaluation was performed after 6 months and then annually for 2 years. Results 14 females (53%) and 13 males (48%) with a diagnosis of GERD (with type I HH) and type II HH were operated upon. The mean age was 46 years (24–75 years) and the mean body mass index (BMI) was 27 (18–32). The range of duration of the preoperative symptoms was 6 months to 2 years. The average operating time dropped from 130 minutes for the first 12 cases to 90 minutes for the last 15 cases. The mean hospital stay was 3 days (range: 2–4 days). In the immediate postoperative period, 72% (n = 18) of the patients reported improvement in the GERD symptoms, while 2 (8%) patients described heartburn (grade I, mild, daily) and 1 (4%) patient described bloating (grade I, daily). A total of 5 patients (20%) reported mild dysphagia to solids in the first 2 postoperative weeks. These symptoms settled down after 2 to 5 weeks of postoperative proton-pump inhibitor (PPI) therapy and by adjusting consistency of oral feeds. There was no conversion to open, and we observed no perioperative mortality. There were no patients who underwent redo surgeries in the series. Conclusion LF is a safe and highly effective procedure for a patient with symptoms of GERD, and it gives long-term relief from the symptoms. Stringent selection criteria are necessary to optimize the results of surgery. Experience is associated with a significant reduction of operating time.

A New Classification for Pathologies of Spinal Meninges, Part 1: Dural Cysts, Dissections, and Ectasias

Neurosurgery ◽  
2017 ◽  
Vol 81 (1) ◽  
pp. 29-44 ◽  
Author(s):  
Jörg Klekamp
Keyword(s):  
Structural Changes ◽  
Long Term Results ◽  
Type I ◽  
Type Ii ◽  
New Classification ◽  
Type Iii ◽  
Dural Sac ◽  
Spinal Cord Herniation ◽  
Dural Defects

Abstract BACKGROUND: The clinical significance of pathologies of the spinal dura is often unclear and their management controversial. OBJECTIVE: To classify spinal dural pathologies analogous to vascular aneurysms, present their symptoms and surgical results. METHODS: Among 1519 patients with spinal space-occupying lesions, 66 patients demonstrated dural pathologies. Neuroradiological and surgical features were reviewed and clinical data analyzed. RESULTS: Saccular dural diverticula (type I, n = 28) caused by defects of both dural layers, dissections between dural layers (type II, n = 29) due to defects of the inner layer, and dural ectasias (type III, n = 9) related to structural changes of the dura were distinguished. For all types, symptoms consisted of local pain followed by signs of radiculopathy or myelopathy, while one patient with dural ectasia presented a low-pressure syndrome and 10 patients with dural dissections additional spinal cord herniation. Type I and type II pathologies required occlusion of their dural defects via extradural (type I) or intradural (type II) approaches. For type III pathologies of the dural sac no surgery was recommended. Favorable results were obtained in all 14 patients with type I and 13 of 15 patients with type II pathologies undergoing surgery. CONCLUSION: The majority of dural pathologies involving root sleeves remain asymptomatic, while those of the dural sac commonly lead to pain and neurological symptoms. Type I and type II pathologies were treated with good long-term results occluding their dural defects, while ectasias of the dural sac (type III) were managed conservatively.

scholarly journals Comprehensive Characterization of Toxoplasma Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Yong Fu ◽  
Xia Cui ◽  
Sai Fan ◽  
Jing Liu ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Toxoplasma Gondii ◽  
Binding Protein ◽  
Ankyrin Repeat ◽  
Type I ◽  
Type Ii ◽  
Content Type ◽  
High K ◽  
Acyl Coenzyme A

ABSTRACT Acyl coenzyme A (CoA)-binding protein (ACBP) can bind acyl-CoAs with high specificity and affinity, thus playing multiple roles in cellular functions. Mitochondria of the apicomplexan parasite Toxoplasma gondii have emerged as key organelles for lipid metabolism and signaling transduction. However, the rationale for how this parasite utilizes acyl-CoA-binding protein to regulate mitochondrial lipid metabolism remains unclear. Here, we show that an ankyrin repeat-containing protein, TgACBP2, is localized to mitochondria and displays active acyl-CoA-binding activities. Dephosphorylation of TgACBP2 is associated with relocation from the plasma membrane to the mitochondria under conditions of regulation of environmental [K+]. Under high [K+] conditions, loss of ACBP2 induced mitochondrial dysfunction and apoptosis-like cell death. Disruption of ACBP2 caused growth and virulence defects in the type II strain but not in type I parasites. Interestingly, mitochondrial association factor-1 (MAF1)-mediated host mitochondrial association (HMA) restored the growth ability of ACBP2-deficient type II parasites. Lipidomics analysis indicated that ACBP2 plays key roles in the cardiolipin metabolism of type II parasites and that MAF1 expression complemented the lipid metabolism defects of ACBP2-deficient type II parasites. In addition, disruption of ACBP2 caused attenuated virulence of Prugniuad (Pru) parasites for mice. Taking the results collectively, these data indicate that ACBP2 is critical for the growth and virulence of type II parasites and for the growth of type I parasites under high [K+] conditions. IMPORTANCE Toxoplasma gondii is one of the most successful human parasites, infecting nearly one-third of the total world population. T. gondii tachyzoites residing within parasitophorous vacuoles (PVs) can acquire fatty acids both via salvage from host cells and via de novo synthesis pathways for membrane biogenesis. However, although fatty acid fluxes are known to exist in this parasite, how fatty acids flow through Toxoplasma lipid metabolic organelles, especially mitochondria, remains unknown. In this study, we demonstrated that Toxoplasma expresses an active ankyrin repeat containing protein TgACBP2 to coordinate cardiolipin metabolism. Specifically, HMA acquisition resulting from heterologous functional expression of MAF1 rescued growth and lipid metabolism defects in ACBP2-deficient type II parasites, manifesting the complementary role of host mitochondria in parasite cardiolipin metabolism. This work highlights the importance of TgACBP2 in parasite cardiolipin metabolism and provides evidence for metabolic association of host mitochondria with T. gondii.

scholarly journals Snow Avalanches and Acoustic Emissions

1983 ◽  
Vol 4 ◽  
pp. 271-276 ◽  
Author(s):  
R. A. Sommerfeld ◽  
H. Gubler
Keyword(s):  
Acoustic Emissions ◽  
Limited Range ◽  
Slope Instability ◽  
Type I ◽  
Type Ii ◽  
Noise Levels ◽  
Active Layers ◽  
Differential Movement ◽  
Emission Activity

Analyses of several years of data show that acoustic emission activity is greater from unstable snowpacks than from stable snowpacks. Two types of signals have been identified: type I spikes and type II long-term elevation of the noise level. It is thought that the type I signals originate from macroscopic cracks. The type II signals may originate from differential movement on shearing surfaces, but this is less certain. Increased noise levels of both types correlate well with slope instability, when the slope stability is known. In some climates the limited range of signal detection might be a significant problem. A foam-mounted geophone set into the snow near active layers appears to be the best sensor available at present.

scholarly journals High prevalence of unusual genotypes of Toxoplasma gondii infection in pork meat samples from Erechim, Southern Brazil

2007 ◽  
Vol 79 (1) ◽  
pp. 111-114 ◽  
Author(s):  
RN Belfort ◽  
Veronique Nussenblatt ◽  
Luiz Rizzo ◽  
Cristina Muccioli ◽  
Claudio Silveira ◽  
...  
Keyword(s):  
Restriction Analysis ◽  
Rflp Analysis ◽  
Type I ◽  
Type Ii ◽  
Molecular Biological Technique ◽  
High Prevalence ◽  
Biological Technique ◽  
Infectious Uveitis ◽  
Toxoplasma Gondii Infection ◽  
Meat Samples

Toxoplasmosis is the most common cause of infectious uveitis in Brazil, with a higher frequency in the South of the country. We have collected samples from porcine tongue and diaphragm obtained in both large and small abattoirs and used molecular biological technique to determine the prevalence of infection and RFLP analysis to type the parasites. Seventeen out of 50 (34%) samples from the diaphragm and 33 out of 50 (66%) samples from the tongue demonstrated a positive PCR reaction for T. gondii and restriction analysis of four of the positive samples revealed that all had a type I genotype at SAG2. However, when other unlinked loci were analyzed, these strains had a type III genotype at markers BTUB, SAG3, and GRA6. One of the strains (8T) had a type II allele at SAG3, indicating it has a combination of alleles normally seen in the clonal lineages. Our sampling indicates a high prevalence of infection and suggests that unusual genotypes of T. gondii are found in Brazil even among domesticated pigs.

Evidence of the three main clonalToxoplasma gondiilineages from wild mammalian carnivores in the UK

Parasitology ◽  
2013 ◽  
Vol 140 (14) ◽  
pp. 1768-1776 ◽  
Author(s):  
A. BURRELLS ◽  
P. M. BARTLEY ◽  
I. A. ZIMMER ◽  
S. ROY ◽  
A. C. KITCHENER ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Rflp Markers ◽  
Type I ◽  
Type Ii ◽  
Red Foxes ◽  
Mammal Species ◽  
Tissue Samples ◽  
Pcr Rflp ◽  
Few Data ◽  
The Uk

SUMMARYToxoplasma gondiiis a zoonotic pathogen defined by three main clonal lineages (types I, II, III), of which type II is most common in Europe. Very few data exist on the prevalence and genotypes ofT. gondiiin the UK. Wildlife can act as sentinel species forT. gondiigenotypes present in the environment, which may subsequently be transmitted to livestock and humans. DNA was extracted from tissue samples of wild British carnivores, including 99 ferrets, 83 red foxes, 70 polecats, 65 mink, 64 badgers and 9 stoats. Parasite DNA was detected using a nested ITS1 PCR specific forT. gondii, PCR positive samples were subsequently genotyped using five PCR–RFLP markers.Toxoplasma gondiiDNA was detected within all these mammal species and prevalence varied from 6·0 to 44·4% depending on the host. PCR–RFLP genotyping identified type II as the predominant lineage, but type III and type I alleles were also identified. No atypical or mixed genotypes were identified within these animals. This study demonstrates the presence of alleles for all three clonal lineages with potential for transmission to cats and livestock. This is the first DNA-based study ofT. gondiiprevalence and genotypes across a broad range of wild British carnivores.

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