CoChat
Sign Up
Cited by 35Toxoplasma gondii Research StudiesCoccidia and coccidiosis researchParasitic infections in humans and animals

The DOI matches its Crossref record.

Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute, Chronic, and Congenital Toxoplasmosis in Mice

Open access
Wang, Jin-Lei, Liang, Qin-Li, Li, Ting-Ting, He, Jun-Jun, Bai, Meng-Jie, Cao, Xue-Zhen, Elsheikha, Hany M, Zhu, Xing-Quan·2020·The Journal of Immunology
DOI 10.4049/jimmunol.1900410
Open this paper in CoChat — free account

Abstract

In this study, we generated a tkl1 deletion mutant in the Toxoplasma gondii type 1 RH (RHΔtkl1) strain and tested the protective efficacies of vaccination using RHΔtkl1 tachyzoites against acute, chronic, and congenital T. gondii infections in Kunming mice. Mice vaccinated with RHΔtkl1 mounted a strong humoral and cellular response as shown by elevated levels of anti–T. gondii–specific IgG, IL-2, IL-12, IFN-γ, and IL-10. All RHΔtkl1-vaccinated mice survived a lethal challenge with 1 × 103 tachyzoites of type 1 RH or ToxoDB#9 (PYS or TgC7) strain as well as 100 cysts or oocysts of Prugniuad strain. All mock-vaccinated plus infected mice have died. Vaccination also protected against cyst- or oocyst-caused chronic infection, reduced vertical transmission caused by oocysts, increased litter size, and maintained body weight of pups born to dams challenged with 10 oocysts on day 5 of gestation. In contrast, all mock-vaccinated plus oocysts-infected dams had aborted, and no fetus has survived. Vaccinated dams remained healthy postinfection, and their brain cyst burden was significantly reduced compared with mock-vaccinated dams infected with oocysts. In vivo depletion of CD4+ T cells, CD8+ T cells, and B cells revealed that CD8+ T cells are involved in the protection of mice against T. gondii infection. Additionally, adoptive transfer of CD8+ T cells from RHΔtkl1-vaccinated mice significantly enhanced the survival of naive mice infected with the pathogenic strain. Together, these data reaffirm the importance of CD8+ T cell responses in future vaccine design for toxoplasmosis and present T. gondii tkl1 gene as a promising vaccine candidate.

Overview

Integrity signals

Registry

Crossref · 10.4049/jimmunol.1900410

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 42

  1. Robert-Gangneux, 2012, Epidemiology of and diagnostic strategies for toxoplasmosis, Clin. Microbiol. Rev., 25, 264, 10.1128/CMR.05013-11 · DOI
  2. Djurković-Djaković, 2013, Pork as a source of human parasitic infection, Clin. Microbiol. Infect., 19, 586, 10.1111/1469-0691.12162 · DOI
  3. Wang, 2017, Prevalence and burden of Toxoplasma gondii infection in HIV-infected people: a systematic review and meta-analysis, Lancet HIV, 4, e177, 10.1016/S2352-3018(17)30005-X · DOI
  4. Sensini, 2006, Toxoplasma gondii infection in pregnancy: opportunities and pitfalls of serological diagnosis, Clin. Microbiol. Infect., 12, 504, 10.1111/j.1469-0691.2006.01444.x · DOI
  5. Dubey, 2016, Toxoplasmosis of Animals and Humans., 10.1201/9781420092370 · DOI
  6. Dunay, 2018, Treatment of toxoplasmosis: historical perspective, animal models, and current clinical practice, Clin. Microbiol. Rev., 31, 10.1128/CMR.00057-17 · DOI
  7. Wang, 2019, Advances in the development of anti-Toxoplasma gondii vaccines: challenges, opportunities, and perspectives, Trends Parasitol., 35, 239, 10.1016/j.pt.2019.01.005 · DOI
  8. Buxton, 1995, A commercial vaccine for ovine toxoplasmosis, Parasitology, 110, S11, 10.1017/S003118200000144X · DOI
  9. Wang, 2016, The past, present, and future of genetic manipulation in Toxoplasma gondii, Trends Parasitol., 32, 542, 10.1016/j.pt.2016.04.013 · DOI
  10. Goswami, 2019, Designer parasites: genetically engineered plasmodium as vaccines to prevent malaria infection, J. Immunol., 202, 20, 10.4049/jimmunol.1800727 · DOI
  11. Singer, 2017, Time for genome editing: next-generation attenuated malaria parasites, Trends Parasitol., 33, 202, 10.1016/j.pt.2016.09.012 · DOI
  12. Khan, 2012, Genetic engineering of attenuated malaria parasites for vaccination, Curr. Opin. Biotechnol., 23, 908, 10.1016/j.copbio.2012.04.003 · DOI
  13. Wang, 2017, Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice, Front. Immunol., 8, 730, 10.3389/fimmu.2017.00730 · DOI · Paper page
  14. Wang, 2018, Live attenuated Pru:Δcdpk2 strain of Toxoplasma gondii protects against acute, chronic, and congenital toxoplasmosis, J. Infect. Dis., 218, 768, 10.1093/infdis/jiy211 · DOI
  15. Ismael, 2006, Mic1-3 knockout of Toxoplasma gondii is a successful vaccine against chronic and congenital toxoplasmosis in mice, J. Infect. Dis., 194, 1176, 10.1086/507706 · DOI
  16. Gigley, 2009, Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th1 host immune responses in the absence of parasite replication, J. Immunol., 182, 1069, 10.4049/jimmunol.182.2.1069 · DOI
  17. Varberg, 2018, TgTKL1 is a unique plant-like nuclear kinase that plays an essential role in acute toxoplasmosis, MBio, 9, 10.1128/mBio.00301-18 · DOI
  18. Liu, 2016, Measurement and analysis of the reproductive performance in six commonly used SPF mice and rats, Chin. J. Comp. Med., 10, 9
  19. Hu, 2018, Differential brain MicroRNA expression profiles after acute and chronic infection of mice with Toxoplasma gondii oocysts, Front. Microbiol., 9, 2316, 10.3389/fmicb.2018.02316 · DOI
  20. Staggs, 2009, Obtaining highly purified Toxoplasma gondii oocysts by a discontinuous cesium chloride gradient, J. Vis. Exp., 33, 1420
  21. Shwab, 2018, Human impact on the diversity and virulence of the ubiquitous zoonotic parasite Toxoplasma gondii, Proc. Natl. Acad. Sci. USA, 115, E6956, 10.1073/pnas.1722202115 · DOI
  22. Howe, 1995, Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease, J. Infect. Dis., 172, 1561, 10.1093/infdis/172.6.1561 · DOI
  23. Carmi, 2015, Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity, Nature, 521, 99, 10.1038/nature14424 · DOI
  24. Ely, 1999, Augmentation of the CD8+ T cell response by IFN-gamma in IL-12-deficient mice during Toxoplasma gondii infection, J. Immunol., 162, 5449, 10.4049/jimmunol.162.9.5449 · DOI
  25. Suzuki, 2010, Removal of Toxoplasma gondii cysts from the brain by perforin-mediated activity of CD8+ T cells, Am. J. Pathol., 176, 1607, 10.2353/ajpath.2010.090825 · DOI
  26. Sayles, 2000, B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii, Infect. Immun., 68, 1026, 10.1128/IAI.68.3.1026-1033.2000 · DOI
  27. Ivanova, 2019, The IL-12- and IL-23-dependent NK cell response is essential for protective immunity against secondary Toxoplasma gondii infection, J. Immunol., 203, 2944, 10.4049/jimmunol.1801525 · DOI
  28. Hwang, 2015, CD8+ T cell immunity in an encephalitis model of Toxoplasma gondii infection, Semin. Immunopathol., 37, 271, 10.1007/s00281-015-0483-7 · DOI
  29. Tsitsiklis, 2019, CD8+ T cell responses to Toxoplasma gondii: lessons from a successful parasite, Trends Parasitol., 35, 887, 10.1016/j.pt.2019.08.005 · DOI
  30. Yap, 2000, Cutting edge: IL-12 is required for the maintenance of IFN-gamma production in T cells mediating chronic resistance to the intracellular pathogen, Toxoplasma gondii, J. Immunol., 165, 628, 10.4049/jimmunol.165.2.628 · DOI
  31. Wilson, 2008, IL-12 signaling drives CD8+ T cell IFN-gamma production and differentiation of KLRG1+ effector subpopulations during Toxoplasma gondii Infection, J. Immunol., 180, 5935, 10.4049/jimmunol.180.9.5935 · DOI
  32. Bao, 2014, The immune potential and immunopathology of cytokine-producing B cell subsets: a comprehensive review, J. Autoimmun., 55, 10, 10.1016/j.jaut.2014.04.001 · DOI
  33. Suzuki, 1988, Interferon-gamma: the major mediator of resistance against Toxoplasma gondii, Science, 240, 516, 10.1126/science.3128869 · DOI
  34. Thiébaut, 2007, Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients’ data, Lancet, 369, 115, 10.1016/S0140-6736(07)60072-5 · DOI
  35. Zhang, 2017, Modulators of the balance between M1 and M2 macrophages during pregnancy, Front. Immunol., 8, 120
  36. Menzies, 2008, Immunological control of congenital toxoplasmosis in the murine model, Immunol. Lett., 115, 83, 10.1016/j.imlet.2007.10.009 · DOI
  37. Borges, 2019, How does toxoplasmosis affect the maternal-foetal immune interface and pregnancy?, Parasite Immunol., 41, 10.1111/pim.12606 · DOI
  38. Abou-Bacar, 2004, Role of gamma interferon and T cells in congenital Toxoplasma transmission, Parasite Immunol., 26, 315, 10.1111/j.0141-9838.2004.00713.x · DOI
  39. Lao, 2015, IL-10 regulate decidual Tregs apoptosis contributing to the abnormal pregnancy with Toxoplasma gondii infection, Microb. Pathog., 89, 210, 10.1016/j.micpath.2015.10.002 · DOI
  40. Yarovinsky, 2014, Innate immunity to Toxoplasma gondii infection, Nat. Rev. Immunol., 14, 109, 10.1038/nri3598 · DOI
  41. Sturge, 2014, Complex immune cell interplay in the gamma interferon response during Toxoplasma gondii infection, Infect. Immun., 82, 3090, 10.1128/IAI.01722-14 · DOI
  42. Pittman, 2015, Long-term relationships: the complicated interplay between the host and the developmental stages of Toxoplasma gondii during acute and chronic infections, Microbiol. Mol. Biol. Rev., 79, 387, 10.1128/MMBR.00027-15 · DOI

Cited by

Sorted by citations

Metadata

Authors
Wang, J.-L., Liang, Q.-L., Li, T.-T., He, J.-J., Bai, M.-J., Cao, X.-Z., Elsheikha, H. M., & Zhu, X.-Q.
Affiliations
  • Lanzhou Veterinary Research Institute (CN)
  • State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou, Gansu Province 730046 ,
  • University of Nottingham (GB)
Corresponding author
He, Jun-Jun
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2020-03
Volume
204
Issue
6
Pages
1562-1570
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.1900410
OpenAlex
W3003301494
Cited by
35
References
0
Citations by year
2026: 4 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 5
FWCI
3.38
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Repository@Nottingham (University of Nottingham) (acceptedVersion)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Coccidia and coccidiosis research
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasitic infections in humans and animals
Keywords
Toxoplasma gondii, toxoplasmosis vaccine, congenital toxoplasmosis, chronic toxoplasmosis, acute toxoplasmosis, vertical transmission, CD8+ T cells, adoptive T cell therapy, humoral and cellular immune response, brain cyst burden, oocysts, vaccine candidate
MeSH terms
Acute Disease, Animals, Chronic Disease, Disease Models, Animal, Female, Humans, Male, Toxoplasma, Toxoplasmosis, Animal, Toxoplasmosis, Congenital, Virulence, Protozoan Proteins, Protozoan Vaccines, Genes, Protozoan, Sequence Deletion, CD8-Positive T-Lymphocytes, Infectious Disease Transmission, Vertical, Adoptive Transfer, Virulence Factors, Mice, Livestock

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review