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

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

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.

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

• Journal Article Type: Article
• Acceptance Date: May 23, 2020
• Online Publication Date: May 30, 2020
• Publication Date: Jul 1, 2020
• Deposit Date: Jul 7, 2020
• Publicly Available Date: Jul 7, 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
• DOI: https://doi.org/10.1016/j.ijmm.2020.151432
• Keywords: Microbiology (medical); Microbiology; Infectious Diseases; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4737319
• 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.