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Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice

Neospora caninum is an apicomplexan parasite that infects many mammals and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles...

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Autores principales: Li, Shan, Zhang, Nan, Liu, Shaoxiong, Li, Jianhua, Liu, Li, Wang, Xiaocen, Li, Xin, Gong, Pengtao, Zhang, Xichen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965954/
https://www.ncbi.nlm.nih.gov/pubmed/33748214
http://dx.doi.org/10.3389/fvets.2021.638173
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author Li, Shan
Zhang, Nan
Liu, Shaoxiong
Li, Jianhua
Liu, Li
Wang, Xiaocen
Li, Xin
Gong, Pengtao
Zhang, Xichen
author_facet Li, Shan
Zhang, Nan
Liu, Shaoxiong
Li, Jianhua
Liu, Li
Wang, Xiaocen
Li, Xin
Gong, Pengtao
Zhang, Xichen
author_sort Li, Shan
collection PubMed
description Neospora caninum is an apicomplexan parasite that infects many mammals and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles (NEVs), can induce effective immune responses and stimulate cytokine expression in mouse peritoneal macrophages. However, whether Nc14-3-3 has a protective effect and its mechanisms are poorly understood. Here, we evaluated the immune responses and protective effects of Nc14-3-3 against exposure to 2 × 10(7) Nc-1 tachyzoites. Antibody (IgG, IgGl, and IgG2a) levels and Th1-type (IFN-γ and IL-12) and Th2-type (IL-4 and IL-10) cytokines in mouse serum, survival rates, survival times, and parasite burdens were detected. In the present study, the immunostimulatory effect of Nc14-3-3 was confirmed, as it triggered Th1-type cytokine (IFN-γ and IL-12) production in mouse serum 2 weeks after the final immunization. Moreover, the immunization of C57BL/6 mice with Nc14-3-3 induced high IgG antibody levels and significant increases in CD8(+) T lymphocytes in the spleens of mice, indicating that the cellular immune response was significantly stimulated. Mouse survival rates and times were significantly prolonged after immunization; the survival rates were 40% for Nc14-3-3 immunization and 60% for NEV immunization, while mice that received GST, PBS, or blank control all died at 13, 9, or 8 days, respectively, after intraperitoneal N. caninum challenge. In addition, qPCR analysis indicated that there was a reduced parasite burden and diminished pathological changes in the mice immunized with Nc14-3-3. Our data demonstrate that vaccination of mice with Nc14-3-3 elicits both cellular and humoral immune responses and provides partial protection against acute neosporosis. Thus, Nc14-3-3 could be an effective antigen candidate for vaccine development for neosporosis.
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spelling pubmed-79659542021-03-18 Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice Li, Shan Zhang, Nan Liu, Shaoxiong Li, Jianhua Liu, Li Wang, Xiaocen Li, Xin Gong, Pengtao Zhang, Xichen Front Vet Sci Veterinary Science Neospora caninum is an apicomplexan parasite that infects many mammals and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles (NEVs), can induce effective immune responses and stimulate cytokine expression in mouse peritoneal macrophages. However, whether Nc14-3-3 has a protective effect and its mechanisms are poorly understood. Here, we evaluated the immune responses and protective effects of Nc14-3-3 against exposure to 2 × 10(7) Nc-1 tachyzoites. Antibody (IgG, IgGl, and IgG2a) levels and Th1-type (IFN-γ and IL-12) and Th2-type (IL-4 and IL-10) cytokines in mouse serum, survival rates, survival times, and parasite burdens were detected. In the present study, the immunostimulatory effect of Nc14-3-3 was confirmed, as it triggered Th1-type cytokine (IFN-γ and IL-12) production in mouse serum 2 weeks after the final immunization. Moreover, the immunization of C57BL/6 mice with Nc14-3-3 induced high IgG antibody levels and significant increases in CD8(+) T lymphocytes in the spleens of mice, indicating that the cellular immune response was significantly stimulated. Mouse survival rates and times were significantly prolonged after immunization; the survival rates were 40% for Nc14-3-3 immunization and 60% for NEV immunization, while mice that received GST, PBS, or blank control all died at 13, 9, or 8 days, respectively, after intraperitoneal N. caninum challenge. In addition, qPCR analysis indicated that there was a reduced parasite burden and diminished pathological changes in the mice immunized with Nc14-3-3. Our data demonstrate that vaccination of mice with Nc14-3-3 elicits both cellular and humoral immune responses and provides partial protection against acute neosporosis. Thus, Nc14-3-3 could be an effective antigen candidate for vaccine development for neosporosis. Frontiers Media S.A. 2021-03-03 /pmc/articles/PMC7965954/ /pubmed/33748214 http://dx.doi.org/10.3389/fvets.2021.638173 Text en Copyright © 2021 Li, Zhang, Liu, Li, Liu, Wang, Li, Gong and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Li, Shan
Zhang, Nan
Liu, Shaoxiong
Li, Jianhua
Liu, Li
Wang, Xiaocen
Li, Xin
Gong, Pengtao
Zhang, Xichen
Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice
title Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice
title_full Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice
title_fullStr Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice
title_full_unstemmed Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice
title_short Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice
title_sort protective immunity against neospora caninum infection induced by 14-3-3 protein in mice
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965954/
https://www.ncbi.nlm.nih.gov/pubmed/33748214
http://dx.doi.org/10.3389/fvets.2021.638173
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