Immune Responses Induced by pVAX/TgERK7 against Toxoplasma gondii Infection in BALB/c Mice
Abstract
Background: Toxoplasma gondii can infect all the warm-blooded vertebrates and cause serious toxoplasmosis. Extracellular signal-regulated kinase 7 in T. gondii (TgERK7) mediated the proliferation of this parasite may be a potential vaccine candidate. Thus, immune responses induced by TgERK7 were investigated in this study using a DNA vaccine strategy.
Methods: pVAX/TgERK7 plasmid was constructed and used to immunize BALB/c mice for three times with two-week intervals. The challenge and the investigation of humoral and cellular immune responses were performed at two weeks post the last immunization, and the survival times of the infected mice were daily recorded until all of them were dead.
Results: The innate immune response with higher concentrations of IFN-γ, TNF-α, IL2 and IL12p70 in sera (P < 0.05), and the adaptive immune responses were evoked by the DNA immunizations, including specific antibody, lymphocyte proliferation, and the CD3e+CD4+ and CD3e+CD8a+ T cell-mediated response effects. Interestingly, no significant difference was detected in their survival times among all the experimental groups of mice that were challenged with GT1 tachyzoites or PRU cysts (P>0.05).
Conclusion: The successive immunizations with pVAX/TgERK7 can provoke the innate and adaptive immune responses of BALB/c mice, whereas the DNA vaccine-induced immunological efficacy is not sufficient for complete protection the host against T. gondii infection.
Yarovinsky F. Innate immunity to Toxoplasma gondii infection. Nat Rev Immunol. 2014;14(2):109-21.
Dubey JP. Toxoplasmosis of animals and humans. Boca Raton, New York: CRC Press Inc., Second, 2010;1-313.
Zhang NZ, Wang M, Xu Y et al. Recent advances in developing vaccines against Toxoplasma gondii: an update. Expert Rev Vaccines. 2015;14(12):1609-21.
Atay O, Skotheim JM. Spatial and temporal signal processing and decision making by MAPK pathways. J Cell Biol. 2017;216(2):317-30.
Lake D, Corrêa SA, Müller J. Negative feedback regulation of the ERK1/2 MAPK pathway. Cell Mol Life Sci. 2016;73(23):4397-413.
Kuhn D, Wiese M. LmxPK4, a mitogen-activated protein kinase kinase homologue of Leishmania mexicana with a potential role in parasite differentiation. Mol Microbiol. 2005;56(5):1169-82.
Bengs F, Scholz A, Kuhn D et al. LmxMPK9, a mitogen-activated protein kinase homologue affects flagellar length in Leishmania mexicana. Mol Microbiol. 2005;55(5):1606-15.
Ellis JG 4th, Davila M, Chakrabarti R. Potential involvement of extracellular signal-regulated kinase 1 and 2 in encystation of a primitive eukaryote, Giardia lamblia. Stage-specific activation and intracellular localization. J Biol Chem. 2003;278(3):1936-45.
Lye YM, Chan M, Sim TS. Pfnek3: an atypical activator of a MAP kinase in Plasmodium falciparum. FEBS Lett. 2006;580(26):6083-92.
Low H, Lye YM, Sim TS. Pfnek3 functions as an atypical MAPKK in Plasmodium falciparum. Biochem Biophys Res Commun. 2007;361(2):439-44.
Lacey MR, Brumlik MJ, Yenni RE et al. Toxoplasma gondii expresses two mitogen-activated protein kinase genes that represent distinct protozoan subfamilies. J Mol Evol. 2007;64(1):4-14.
Huang H, Ma YF, Bao Y et al. Molecular cloning and characterization of mitogen-activated protein kinase 2 in Toxoplasma gondii. Cell Cycle. 2011;10(20):3519-26.
Brumlik MJ, Wei S, Finstad K et al. Identification of a novel mitogen-activated protein kinase in Toxoplasma gondii. Int J Parasitol. 2004;34(11):1245-54.
Cao L, Wang Z, Wang S et al. Deletion of mitogen-activated protein kinase 1 inhibits development and growth of Toxoplasma gondii. Parasitol Res. 2016;115(2):797-805.
Li ZY, Wang ZD, Huang SY et al. TgERK7 is involved in the intracellular proliferation of Toxoplasma gondii. Parasitol Res. 2016;115(9):3419-24.
Menzies FM, Henriquez FL, Roberts CW. Immunological control of congenital toxoplasmosis in the murine model. Immunol Lett. 2008;115(2):83-9.
Li ZY, Chen J, Petersen E et al. Synergy of mIL-21 and mIL-15 in enhancing DNA vaccine efficacy against acute and chronic Toxoplasma gondii infection in mice. Vaccine. 2014;32(25):3058-65.
Antunes DA, Devaurs D, Kavraki LE. Understanding the challenges of protein flexibility in drug design. Expert Opin Drug Discov. 2015;10(12):1301-13.
Berzofsky JA. Intrinsic and extrinsic factors in protein antigenic structure. Science. 1985;229(4717):932-40.
Mazaheri N, Dalimi A, Pirestani M et al. Construction and identification of a recombinant plasmid encoding Echinococcus granulosus oncosphere antigen (EG95). Iran J Parasitol. 2017;12(4):490-7.
Yuan ZG, Zhang XX, Lin RQ et al. Protective effect against toxoplasmosis in mice induced by DNA immunization with gene encoding Toxoplasma gondii ROP18. Vaccine. 2011;29(38):6614-9.
Chen J, Huang SY, Zhou DH et al. DNA immunization with eukaryotic initiation factor-2α of Toxoplasma gondii induces protective immunity against acute and chronic toxoplasmosis in mice. Vaccine. 2013;31(52):6225-31.
Bounous DI, Campagnoli RP, Brown J. Comparison of MTT colorimetric assay and tritiated thymidine uptake for lymphocyte proliferation assays using chicken splenocytes. Avian Dis. 1992;36(4):1022-7.
Weiss LM, Dubey JP. Toxoplasmosis: a history of clinical observations. Int J Parasitol. 2009;39(8):895-901.
Sibley LD. Intracellular parasite invasion strategies. Science. 2004;304(5668):248-53.
Kur J, Holec-Gasior L, Hiszczyńska-Sawicka E. Current status of toxoplasmosis vaccine development. Expert Rev Vaccines. 2009;8(6):791-808.
Garcia JL. Vaccination concepts against Toxoplasma gondii. Expert Rev Vaccines. 2009;8(2):215-25.
Gurunathan S, Klinman DM, Seder RA. DNA vaccines: immunology, application, and optimization. Annu Rev Immunol. 2000;18:927-74.
Dupont CD, Christian DA, Hunter CA. Immune response and immunopathology during toxoplasmosis. Semin Immunopathol. 2012;34(6):793-813.
Gazzinelli RT, Wysocka M, Hayashi S et al. Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol. 1994;153(6):2533-43.
Bliss SK, Marshall AJ, Zhang Y et al. Human polymorphonuclear leukocytes produce IL-12, TNF-alpha, and the chemokines macrophage-inflammatory protein-1 alpha and -1 beta in response to Toxoplasma gondii antigens. J Immunol. 1999;162(12):7369-75.
Strack A, Asensio VC, Campbell IL et al. Chemokines are differentially expressed by astrocytes, microglia and inflammatory leukocytes in Toxoplasma encephalitis and critically regulated by interferon-gamma. Acta Neuropathol. 2002;103(5):458-68.
Malla N, Goyal K, Dhanda RS et al. Immunity in urogenital protozoa. Parasite Immunol. 2014;36(9):400-8.
Blanchard N, Dunay IR, Schlüter D. Persistence of Toxoplasma gondii in the central nervous system: a fine-tuned balance between the parasite, the brain and the immune system. Parasite Immunol. 2015;37(3):150-8.
Ni G, Liao Z, Chen S et al. Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice. BMC Immunol. 2017;18(1):40.
Mitchell RE, Hassan M, Burton BR et al. IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation. Sci Rep. 2017;7(1):11315.
Correa D, Cañedo-Solares I, Ortiz-Alegría LB et al. Congenital and acquired toxoplasmosis: diversity and role of antibodies in different compartments of the host. Parasite Immunol. 2007;29(12):651-60.
Kang H, Remington JS, Suzuki Y. Decreased resistance of B cell-deficient mice to infection with Toxoplasma gondii despite unimpaired expression of IFN-gamma, TNF-alpha, and inducible nitric oxide synthase. J Immunol. 2000;164(5):2629-34.
Chen J, Huang SY, Li ZY et al. Protective immunity induced by a DNA vaccine expressing eIF4A of Toxoplasma gondii against acute toxoplasmosis in mice. Vaccine. 2013;31(13):1734-9.
Jongert E, Lemiere A, Van Ginderachter J et al. Functional characterization of in vivo effector CD4(+) and CD8(+) T cell responses in acute toxoplasmosis: an interplay of IFN-gamma and cytolytic T cells. Vaccine. 2010;28(13):2556-64.
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Issue | Vol 14 No 4 (2019) | |
Section | Original Article(s) | |
DOI | https://doi.org/10.18502/ijpa.v14i4.2097 | |
Keywords | ||
Toxoplasma gondii Toxoplasmosis ERK7 DNA vaccine Immune response |
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