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Immunostimulatory efficacy and protective potential of putative TgERK7 protein in mice experimentally infected by Toxoplasma gondii

Li, Zhong Yuan; Guo, Hai Ting; Calderón-Mantilla, Guillermo; He, Jun Jun; Wang, Jin Lei; Bonev, Boyan B.; Zhu, Xing Quan; Elsheikha, Hany M.

Authors

Zhong Yuan Li

Hai Ting Guo

Guillermo Calderón-Mantilla

Jun Jun He

Jin Lei Wang

Xing Quan Zhu



Abstract

© 2020 The Author(s) The extracellular signal-regulated kinases (ERKs) serve as important determinants of cellular signal transduction pathways, and hence may play important roles during infections. Previous work suggested that putative ERK7 of Toxoplasma gondii is required for efficient intracellular replication of the parasite. However, the antigenic and immunostimulatory properties of TgERK7 protein remain unknown. The objective of this study was to produce a recombinant TgERK7 protein in vitro and to evaluate its effect on the induction of humoral and T cell-mediated immune responses against T. gondii infection in BALB/c mice. Immunization using TgERK7 mixed with Freund's adjuvants significantly increased the ratio of CD3e+CD4+ T/CD3e+CD8a+ T lymphocytes in spleen and elevated serum cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-12p70, IL-23, MCP-1, and TNF-α) in immunized mice compared to control mice. On the contrary, immunization did not induce high levels of serum IgG antibodies. Five predicted peptides of TgERK7 were synthesized and conjugated with KLH and used to analyze the antibody specificity in the sera of immunized mice. We detected a progressive increase in the antibody level only against TgERK7 peptide A (DEVDKHVLRKYD). Antibody raised against this peptide significantly decreased intracellular proliferation of T. gondii in vitro, suggesting that peptide A can potentially induce a protective antibody response. We also showed that immunization improved the survival rate of mice challenged with a virulent strain and significantly reduced the parasite cyst burden within the brains of chronically infected mice. Our data show that TgERK7-based immunization induced TgERK7 peptide A-specific immune responses that can impart protective immunity against T. gondii infection. The therapeutic potential of targeting ERK7 signaling pathway for future toxoplasmosis treatment is warranted.

Journal Article Type Article
Publication Date Jul 1, 2020
Journal International Journal of Medical Microbiology
Print ISSN 1438-4221
Electronic ISSN 1618-0607
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 310
Issue 5
APA6 Citation Li, Z. Y., Guo, H. T., Calderón-Mantilla, G., He, J. J., Wang, J. L., Bonev, B. B., …Elsheikha, H. M. (2020). Immunostimulatory efficacy and protective potential of putative TgERK7 protein in mice experimentally infected by Toxoplasma gondii. International Journal of Medical Microbiology, 310(5), https://doi.org/10.1016/j.ijmm.2020.151432
DOI https://doi.org/10.1016/j.ijmm.2020.151432
Keywords Microbiology (medical); Microbiology; Infectious Diseases; General Medicine
Publisher URL https://www.sciencedirect.com/science/article/pii/S1438422120300424
Additional Information This article is maintained by: Elsevier; Article Title: Immunostimulatory efficacy and protective potential of putative TgERK7 protein in mice experimentally infected by Toxoplasma gondii; Journal Title: International Journal of Medical Microbiology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ijmm.2020.151432; Content Type: article; Copyright: © 2020 The Author(s). Published by Elsevier GmbH.

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