scholarly journals RHΔgra17Δnpt1 Strain of Toxoplasma gondii Elicits Protective Immunity Against Acute, Chronic and Congenital Toxoplasmosis in Mice

2020 ◽  
Vol 8 (3) ◽  
pp. 352 ◽  
Author(s):  
Qin-Li Liang ◽  
Li-Xiu Sun ◽  
Hany M. Elsheikha ◽  
Xue-Zhen Cao ◽  
Lan-Bi Nie ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Cellular Response ◽  
Protective Efficacy ◽  
Interleukin 2 ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
Dense Granule ◽  
Lethal Challenge ◽  
Double Deletion ◽  
Brain Cysts

In the present study, a dense granule protein 17 (gra17) and novel putative transporter (npt1) double deletion mutant of Toxoplasma gondii RH strain was engineered. The protective efficacy of vaccination using RHΔgra17Δnpt1 tachyzoites against acute, chronic, and congenital toxoplasmosis was studied in a mouse model. Immunization using RHΔgra17Δnpt1 induced a strong humoral and cellular response, as indicated by the increased levels of anti-T. gondii specific IgG, interleukin 2 (IL-2), IL-10, IL-12, and interferon-gamma (IFN-γ). Vaccinated mice were protected against a lethal challenge dose (103 tachyzoites) of wild-type homologous (RH) strain and heterologous (PYS and TgC7) strains, as well as against 100 tissue cysts or oocysts of Pru strain. Vaccination also conferred protection against chronic infection with 10 tissue cysts or oocysts of Pru strain, where the numbers of brain cysts in the vaccinated mice were significantly reduced compared to those detected in the control (unvaccinated + infected) mice. In addition, vaccination protected against congenital infection with 10 T. gondii Pru oocysts (administered orally on day 5 of gestation) as shown by the increased litter size, survival rate and the bodyweight of pups born to vaccinated dams compared to those born to unvaccinated + infected dams. The brain cyst burden of vaccinated dams was significantly lower than that of unvaccinated dams infected with oocysts. Our data show that T. gondii RHΔgra17Δnpt1 mutant strain can protect mice against acute, chronic, and congenital toxoplasmosis by balancing inflammatory response with immunogenicity.

scholarly journals Resistance to ChronicToxoplasma gondiiInfection Induced by a DNA Vaccine Expressing GRA16

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Ling-Ying Hu ◽  
Nian-Zhang Zhang ◽  
Fu-Kai Zhang ◽  
Meng Wang ◽  
Qi Gao ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Cellular Response ◽  
Protective Efficacy ◽  
Dense Granule ◽  
Human Beings ◽  
Igg Antibody ◽  
Lethal Challenge ◽  
Specific Igg ◽  
Brain Cysts ◽  
Further Development

Toxoplasma gondiican infect all warm-blooded animals including human beings.T. gondiidense granule protein 16 (TgGRA16) as a crucial virulence factor could modulate the host gene expression. Here, a DNA vaccine expressing TgGRA16 was constructed to explore the protective efficacy againstT. gondiiinfection in Kunming mice. The immune responses induced by pVAX-GRA16 were also evaluated. Mice immunized with pVAX-GRA16 could elicit higher levels of specific IgG antibody and strong cellular response compared to those in controls. The DNA vaccination significantly increased the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) and the percentages of CD4+ and CD8+ T cells in mice. After lethal challenge, mice immunized with pVAX-GRA16 (8.4±0.78days) did not show a significant longer survival time than that in controls (7.1±0.30days) (p>0.05). However, in chronic toxoplasmosis model (administration of 10 brain cysts of PRU strain orally), numbers of tissue cysts in mice immunized with pVAX-GRA16 were significantly reduced compared to those in controls (p<0.05) and the rate of reduction could reach 43.89%. The results indicated that the TgGRA16 would be a promising vaccine candidate for further development of effective epitope-based vaccines against chronicT. gondiiinfection in mice.

scholarly journals Incidence of congenital toxoplasmosis in southern Brazil: a prospective study

2003 ◽  
Vol 45 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Liége Mozzatto ◽  
Renato Soibelmann Procianoy
Keyword(s):  
Toxoplasma Gondii ◽  
Gestational Age ◽  
Newborn Infants ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
First Trimester ◽  
Laboratory Diagnosis ◽  
Anthropometric Measures ◽  
Maternal Characteristics ◽  
The Town

The study aimed to determine the incidence of congenital infection by Toxoplasma gondii and to describe neonatal and maternal characteristics regarding newborn infants treated at a teaching hospital in the town of Passo Fundo, State of Rio Grande do Sul, Brazil. Cord blood samples collected from 1,250 live newborns were analyzed. The laboratory diagnosis was established by the detection of Toxoplasma gondii IgM using an enzyme linked fluorescent assay. Gestational age, intrauterine growth, anthropometric measures, and prenatal characteristics were assessed. The incidence of congenital toxoplasmosis at birth was 8/10,000 (95%CI 0.2-44.5). Mean birthweight was 3,080 ± 215.56 grams and mean gestational age was 38.43 ± 1.88 weeks. With regard to prenatal care, 58% of the pregnant patients visited their doctors five times or more and 38.9% were serologically tested for toxoplasmosis in the first trimester of pregnancy. The incidence of congenital toxoplasmosis was similar to that found in most studies conducted in our country and abroad. Our study sample is representative of the town of Passo Fundo and therefore it is possible to consider the frequency observed as the prevalence of the disease in this town during the study period.

scholarly journals Protective Immunity Induced byToxoplasma gondiiRhoptry Protein 16 against Toxoplasmosis in Mice

2010 ◽  
Vol 18 (1) ◽  
pp. 119-124 ◽  
Author(s):  
Zi-Guo Yuan ◽  
Xiu-Xiang Zhang ◽  
Xian-Hui He ◽  
Eskild Petersen ◽  
Dong-Hui Zhou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cellular Response ◽  
Interleukin 2 ◽  
Cell Interaction ◽  
Eukaryotic Expression ◽  
Human Beings ◽  
Survival Times ◽  
Lymphoproliferative Response ◽  
Lethal Challenge ◽  
High Level

ABSTRACTToxoplasma gondiican infect a large variety of domestic and wild animals and human beings, sometimes causing severe pathology. Rhoptries are involved inT. gondiiinvasion and host cell interaction and have been implicated as important virulence factors. In this study, we constructed a DNA vaccine expressing rhoptry protein 16 (ROP16) ofT. gondiiand evaluated the immune responses it induced in Kunming mice. The gene sequence encoding ROP16 was inserted into the eukaryotic expression vector pVAX I. We immunized Kunming mice intramuscularly. After immunization, we evaluated the immune response using a lymphoproliferative assay, cytokine and antibody measurements, and the survival times of mice challenged lethally. The results showed that mice immunized with pVAX-ROP16 developed a high level of specific antibody responses againstT. gondiiROP16 expressed inEscherichia coli, a strong lymphoproliferative response, and significant levels of gamma interferon (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 production compared with results for other mice immunized with either empty plasmid or phosphate-buffered saline, respectively. The results showed that pVAX-ROP16 induces significant humoral and cellular Th1 immune responses. After lethal challenge, the mice immunized with pVAX-ROP16 showed a significantly (P< 0.05) prolonged survival time (21.6 ± 9.9 days) compared with control mice, which died within 7 days of challenge. Our data demonstrate, for the first time, that ROP16 triggers a strong humoral and cellular response againstT. gondiiand that ROP16 is a promising vaccine candidate against toxoplasmosis, worth further development.

scholarly journals The development of the Sabin–Pinkerton triad despite prenatal screening for congenital toxoplasmosis

2021 ◽  
Vol 17 (3) ◽  
pp. 270-274
Author(s):  
Urszula Dryja ◽  
◽  
Anna Niwald ◽  
Ewa Majda-Stanisławska ◽  
◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Prenatal Screening ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
First Trimester ◽  
Imaging Findings ◽  
Pregnant Mother ◽  
First Trimester Of Pregnancy ◽  
Toxoplasma Gondii Infection ◽  
Antiparasitic Treatment

The paper presents a case of a boy who developed the symptoms of congenital toxoplasmosis: hydrocephalus, retinitis, choroiditis and intracranial calcifications (the Sabin–Pinkerton triad). Despite prenatal screening in the first trimester of pregnancy (in accordance with the guidelines of the Ministry of Health), which indicated the diagnosis of asymptomatic primary Toxoplasma gondii infection in the pregnant mother, no antiparasitic therapy was used. The presented serological and imaging findings, as well as specialist consultations confirm the intensified effects of congenital infection in the child. Although the child was put on anti-toxoplasma therapy immediately after birth, he developed severe psychophysical development disorders. The paper discusses recommendations for maternal diagnosis and antiparasitic treatment that could have prevented the full-blown congenital toxoplasmosis in the described patient.

scholarly journals Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Keon-Woong Yoon ◽  
Ki-Back Chu ◽  
Hae-Ji Kang ◽  
Min-Ju Kim ◽  
Gi-Deok Eom ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Recombinant Baculovirus ◽  
Oral Immunization ◽  
Challenge Infection ◽  
Antibody Responses ◽  
Physical Contact ◽  
Lethal Challenge ◽  
Iga Antibody

Pathogens require physical contact with the mucosal surface of the host organism to initiate infection and as such, vaccines eliciting both mucosal and systemic immune responses would be promising. Studies involving the use of recombinant baculoviruses (rBVs) as mucosal vaccines are severely lacking despite their inherently safe nature, especially against pathogens of global importance such as Toxoplasma gondii. Here, we generated rBVs displaying T. gondii rhoptry protein 4 (ROP4) and evaluated their protective efficacy in BALB/c mice following immunization via intranasal (IN) and oral routes. IN immunization with the ROP4-expressing rBVs elicited higher levels of parasite-specific IgA antibody responses compared to oral immunization. Upon challenge infection with a lethal dose of T. gondii ME49, IN immunization elicited significantly higher parasite-specific antibody responses in the mucosal tissues such as intestines, feces, vaginal samples, and brain than oral immunization. Marked increases in IgG and IgA antibody-secreting cell (ASC) responses were observed from intranasally immunized mice. IN immunization elicited significantly enhanced induction of CD4+, CD8+ T cells, and germinal center B (GC B) cell responses from secondary lymphoid organs while limiting the production of the inflammatory cytokines IFN-γ and IL-6 in the brain, all of which contributed to protecting mice against T. gondii lethal challenge infection. Our findings suggest that IN delivery of ROP4 rBVs induced better mucosal and systemic immunity against the lethal T. gondii challenge infection compared to oral immunization.

scholarly journals Studies on a murine model of congenital toxoplasmosis: vertical disease transmission only occurs in BALB/c mice infected for the first time during pregnancy

Parasitology ◽  
1992 ◽  
Vol 104 (1) ◽  
pp. 19-23 ◽  
Author(s):  
C. W. Roberts ◽  
J. Alexander
Keyword(s):  
Toxoplasma Gondii ◽  
Murine Model ◽  
Disease Transmission ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
Tissue Cyst ◽  
First Time

SUMMARYThe incidence of congenital toxoplasmosis was determined by an ELISA in the litters of BALB/c mice which had been infected 8 weeks before mating, on day 12 of pregnancy, or on both these occasions. Of those mice given the infection for the first time on day 12 of pregnancy, 5 out of 6 gave birth to infected litters with approximately 50% of the individuals in each litter being infected. BALB/c mice which had been infected 8 weeks before mating did not give birth to infected litters, even if they were reinfected on day 12 of pregnancy. Following infection BALB/c mice were found to harbour significantly fewer tissue cysts than the congenic H-2 derivative BALB/K strain. However, chronically infected BALB/K mice also failed to produce infected litters, indicating that tissue cyst burden in the dam did not influence congenital infection at least on the BALB background. This study demonstrates that BALB/c dams chronically infected withToxoplasma gondii, have immunity capable of protecting their embryos from congenital infection, even if the dams are reinfected during pregnancy. Our results demonstrate that the BALB/c mouse can be used as a model of human or ovine congenitalT. gondiiinfection suitable for testing putative vaccines.

Toxoplasma gondii

2018 ◽  
Author(s):  
Rima McLeod ◽  
Kelsey Wheeler ◽  
Pauline Levigne ◽  
Kenneth Boyer
Keyword(s):  
Toxoplasma Gondii ◽  
Correct Diagnosis ◽  
Fetal Loss ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
Screening Programs ◽  
Fetal Infection ◽  
Potential Risks ◽  
Mother To Child ◽  
The Brain

Mother-to-child transmission (MTCT) of the parasite Toxoplasma gondii can result in congenital toxoplasmosis. Untreated congenital toxoplasmosis presents considerable potential risks to patients and costs for society, with manifestations recurring throughout life. Infection with T. gondii, acquired at any time during pregnancy can damage the fetus, but especially during early gestation. Fetal infection with T. gondii can cause fetal loss, intrauterine growth retardation, and damage to organs (especially the brain and eyes). Treatment with pyrimethamine and sulfadiazine improves manifestations of active infection in the fetus, congenital infection in infants, and recurrent disease when manifested later in life in those congenitally infected. Key components of the prevention and treatment of congenital toxoplasmosis include prompt, correct diagnosis and treatment with effective anti–T. gondii medications. Several countries have gestational screening programs to detect newly acquired T. gondii infections. In the future, development of new medications, including those for chronic infection, and vaccines for prevention will be important.

scholarly journals Protective Efficacy of a Toxoplasma gondii Rhoptry Protein 13 Plasmid DNA Vaccine in Mice

2012 ◽  
Vol 19 (12) ◽  
pp. 1916-1920 ◽  
Author(s):  
Pei-Yuan Wang ◽  
Zi-Guo Yuan ◽  
Eskild Petersen ◽  
Jie Li ◽  
Xiu-Xiang Zhang ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Dna Vaccine ◽  
Cellular Response ◽  
Protective Efficacy ◽  
Eukaryotic Expression ◽  
Economic Losses ◽  
Type I ◽  
Content Type ◽  
Strain Type ◽  
Rhoptry Protein

ABSTRACTToxoplasma gondiiis an obligate intracellular parasite infecting humans and other warm-blooded animals, resulting in serious public health problems and economic losses worldwide. Rhoptries are involved inT. gondiiinvasion and host cell interaction and have been implicated as important virulence factors. In the present study, a DNA vaccine expressing rhoptry protein 13 (ROP13) ofT. gondiiinserted into eukaryotic expression vector pVAX I was constructed, and the immune protection it induced in Kunming mice was evaluated. Kunming mice were immunized intramuscularly with pVAX-ROP13 and/or with interleukin-18 (IL-18). Then, we evaluated the immune response using a lymphoproliferative assay, cytokine and antibody measurements, and the survival times of mice challenged with the virulentT. gondiiRH strain (type I) and the cyst-forming PRU strain (type II). The results showed that pVAX-ROP13 alone or with pVAX/IL-18 induced a high level of specific anti-T. gondiiantibodies and specific lymphocyte proliferative responses. Coinjection of pVAX/IL-18 significantly increased the production of gamma interferon (IFN-γ), IL-2, IL-4, and IL-10. Further, challenge experiments showed that coimmunization of pVAX-ROP13 with pVAX/IL-18 significantly (P< 0.05) increased survival time (32.3 ± 2.7 days) compared with pVAX-ROP13 alone (24.9 ± 2.3 days). Immunized mice challenged withT. gondiicysts (strain PRU) had a significant reduction in the number of brain cysts, suggesting that ROP13 could trigger a strong humoral and cellular response againstT. gondiicyst infection and that it is a potential vaccine candidate against toxoplasmosis, which provided the foundation for further development of effective vaccines againstT. gondii.

scholarly journals TOKSOPLASMOSIS OKULAR KONGENITAL

2017 ◽  
Vol 17 (2) ◽  
pp. 133-139
Author(s):  
Saiful Basri
Keyword(s):  
Toxoplasma Gondii ◽  
Pregnant Women ◽  
Clinical Manifestation ◽  
Early Treatment ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
Ocular Toxoplasmosis ◽  
Infectious Process ◽  
Serologic Testing

Abstrak. Infeksi toksoplasmosis pada ibu dalam masa kehamilan dapat menyebabkan infeksi kongenital terhadap janin yang akan mengakibatkan  kebutaan pada waktu bayi. Diperkirakan 0,5%-1% wanita hamil di dunia berpotensi terinfeksi kuman Toksoplasma gondii. Manifestasi klinis  pada toksoplasmosis okular kongenital adalah retinokoroiditis, paling banyak terletak di polus posterior. Diagnosis tokosoplasmosis okular kongenital ditegakkan dari hasil pemeriksaan klinis dengan pemeriksaan funduskopi dan serologi anak sekaligus dengan ibunya. Pada 75% bayi dengan infeksi congenital akan menunjukkan titer IgM antibodi anti-Toxoplasma yang positif. Penanganan yang lebih cepat akan mencegah pejalaran proses infeksi and kelainan perkembangan pada anak.(JKS 2017; 2: 139-149)Kata kunci : toksoplasmosis okular congenital, Toksoplasma gondii, retinokoroiditisAbstract. Toxoplasmosis infection during pregnancy can cause congenital infection and manifest as blindness in the infant. Worldwide, about 0,5%-1% of pregnant women become contaminated by Toxoplasma gondii. Clinical manifestation of congenital ocular toxoplasmosis is retinochoroiditis, mostly at posterior pole.The diagnosis of congenital ocular toxoplasmosis is established clinically by funduscopy examination and serologic testing of neonate together with his/her mother. Anti-Toxoplasma antibodies of the IgM are found in 75% of infants with congenital toxoplasmosis. Early treatment may prevent the futher progress of the of the infectious process and the development disorders in children. (JKS 2017; 2: 139-149)Keywords : congenital ocular toxoplasmosis, Toxoplasma gondii, retinochoroiditis,

scholarly journals Secreted Effectors Modulating Immune Responses to Toxoplasma gondii

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 988
Author(s):  
Tadakimi Tomita ◽  
Rebekah B. Guevara ◽  
Lamisha M. Shah ◽  
Andrews Y. Afrifa ◽  
Louis M. Weiss
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Parasitophorous Vacuole ◽  
Congenital Infection ◽  
Dense Granule ◽  
Obligate Intracellular ◽  
Host Cytoplasm ◽  
Life Threatening ◽  
Intracellular Milieu

Toxoplasma gondii is an obligate intracellular parasite that chronically infects a third of humans. It can cause life-threatening encephalitis in immune-compromised individuals. Congenital infection also results in blindness and intellectual disabilities. In the intracellular milieu, parasites encounter various immunological effectors that have been shaped to limit parasite infection. Parasites not only have to suppress these anti-parasitic inflammatory responses but also ensure the host organism’s survival until their subsequent transmission. Recent advancements in T. gondii research have revealed a plethora of parasite-secreted proteins that suppress as well as activate immune responses. This mini-review will comprehensively examine each secreted immunomodulatory effector based on the location of their actions. The first section is focused on secreted effectors that localize to the parasitophorous vacuole membrane, the interface between the parasites and the host cytoplasm. Murine hosts are equipped with potent IFNγ-induced immune-related GTPases, and various parasite effectors subvert these to prevent parasite elimination. The second section examines several cytoplasmic and ER effectors, including a recently described function for matrix antigen 1 (MAG1) as a secreted effector. The third section covers the repertoire of nuclear effectors that hijack transcription factors and epigenetic repressors that alter gene expression. The last section focuses on the translocation of dense-granule effectors and effectors in the setting of T. gondii tissue cysts (the bradyzoite parasitophorous vacuole).

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