Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites
Background: Previous studies showed that a naturally attenuated strain from Trypanosoma cruzi triggers an immune response mainly related to a Th2-type profile. Albeit this, a strong protection against virulent challenge was obtained after priming mice with this attenuated strain. However, this pro...
| Autores principales: | , , , , , , |
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| Formato: | info:ar-repo/semantics/artículo |
| Lenguaje: | Inglés |
| Publicado: |
BioMed Central
2018
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12123/2884 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702110/ |
| _version_ | 1855035044291149824 |
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| author | Pérez Brandan, Cecilia María Mesías, Andrea Cecilia Parodi Ramoneda, Cecilia María Cimino, Rubén Oscar Perez Brandan, Carolina Diosque, Patricio Basombrío, Miguel Angel Manuel |
| author_browse | Basombrío, Miguel Angel Manuel Cimino, Rubén Oscar Diosque, Patricio Mesías, Andrea Cecilia Parodi Ramoneda, Cecilia María Perez Brandan, Carolina Pérez Brandan, Cecilia María |
| author_facet | Pérez Brandan, Cecilia María Mesías, Andrea Cecilia Parodi Ramoneda, Cecilia María Cimino, Rubén Oscar Perez Brandan, Carolina Diosque, Patricio Basombrío, Miguel Angel Manuel |
| author_sort | Pérez Brandan, Cecilia María |
| collection | INTA Digital |
| description | Background: Previous studies showed that a naturally attenuated strain from Trypanosoma cruzi triggers an immune
response mainly related to a Th2-type profile. Albeit this, a strong protection against virulent challenge was
obtained after priming mice with this attenuated strain. However, this protection is not enough to completely
clear parasites from the host. In T. cruzi infection, early Interferon-gamma (IFN-γ) is critical to lead type 1
responses able to control intracellular parasites. Therefore we evaluated whether the co-administration of a
plasmid encoding murine IFN-γ could modify the immune response induced by infection with attenuated
parasites and improve protection against further infections.
Methods: C57BL/6J mice were infected intraperitoneally with three doses of live attenuated parasites in
combination with plasmid pVXVR-mIFN-γ. Before each infection dose, sera samples were collected for
parasite specific antibodies determination and cytokine quantification. To evaluate the recall response to T.
cruzi, mice were challenged with virulent parasites 30 days after the last dose and parasite load in
peripheral blood and heart was evaluated.
Results: As determined by ELISA, significantly increase in T. cruzi specific antibodies response was detected in the group
in which pVXVR-mIFN-γ was incorporated, with a higher predominance of IgG2a subtype in comparison to the group of
mice only inoculated with attenuated parasites. At our limit of detection, serum levels of IFN-γ were not
detected, however a slight decrease in IL-10 concentrations was observed in groups in which pVXVR-mIFN-γ
was supplemented. To analyze if the administration of pVXVR-mIFN-γ has any beneficial effect in protection
against subsequent infections, all experimental groups were submitted to a lethal challenge with virulent
bloodstream trypomastigotes. Similar levels of challenge parasites were detected in peripheral blood and
heart of mice primed with attenuated parasites alone or combined with plasmid DNA. Expansion of IgG
antibodies was not significant in TCC+ pVXVR-mIFN-γ; however, the overall tendency to sustain a Th2
profile was maintained.
Conclusions: Overall, these results suggest that administration of plasmid pVXVR-mIFN-γ could have beneficial effects
on host specific antibody production in response to T. cruzi attenuated infection; however, this outcome is not reflected
in an improved protection against further virulent infections. |
| format | info:ar-repo/semantics/artículo |
| id | INTA2884 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
| publisher | BioMed Central |
| publisherStr | BioMed Central |
| record_format | dspace |
| spelling | INTA28842018-07-26T13:27:14Z Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites Pérez Brandan, Cecilia María Mesías, Andrea Cecilia Parodi Ramoneda, Cecilia María Cimino, Rubén Oscar Perez Brandan, Carolina Diosque, Patricio Basombrío, Miguel Angel Manuel Trypanosoma Cruzi Infección Experimental Respuesta Inmunológica Vectores Plásmidos Plasmid Vectors Immune Response Experimental Infection IFN-γ Plasmid pVXVR-mIFN-y Background: Previous studies showed that a naturally attenuated strain from Trypanosoma cruzi triggers an immune response mainly related to a Th2-type profile. Albeit this, a strong protection against virulent challenge was obtained after priming mice with this attenuated strain. However, this protection is not enough to completely clear parasites from the host. In T. cruzi infection, early Interferon-gamma (IFN-γ) is critical to lead type 1 responses able to control intracellular parasites. Therefore we evaluated whether the co-administration of a plasmid encoding murine IFN-γ could modify the immune response induced by infection with attenuated parasites and improve protection against further infections. Methods: C57BL/6J mice were infected intraperitoneally with three doses of live attenuated parasites in combination with plasmid pVXVR-mIFN-γ. Before each infection dose, sera samples were collected for parasite specific antibodies determination and cytokine quantification. To evaluate the recall response to T. cruzi, mice were challenged with virulent parasites 30 days after the last dose and parasite load in peripheral blood and heart was evaluated. Results: As determined by ELISA, significantly increase in T. cruzi specific antibodies response was detected in the group in which pVXVR-mIFN-γ was incorporated, with a higher predominance of IgG2a subtype in comparison to the group of mice only inoculated with attenuated parasites. At our limit of detection, serum levels of IFN-γ were not detected, however a slight decrease in IL-10 concentrations was observed in groups in which pVXVR-mIFN-γ was supplemented. To analyze if the administration of pVXVR-mIFN-γ has any beneficial effect in protection against subsequent infections, all experimental groups were submitted to a lethal challenge with virulent bloodstream trypomastigotes. Similar levels of challenge parasites were detected in peripheral blood and heart of mice primed with attenuated parasites alone or combined with plasmid DNA. Expansion of IgG antibodies was not significant in TCC+ pVXVR-mIFN-γ; however, the overall tendency to sustain a Th2 profile was maintained. Conclusions: Overall, these results suggest that administration of plasmid pVXVR-mIFN-γ could have beneficial effects on host specific antibody production in response to T. cruzi attenuated infection; however, this outcome is not reflected in an improved protection against further virulent infections. EEA Salta Fil: Pérez Brandan, Cecilia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina Fil: Mesías, Andrea Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina Fil: Parodi Ramoneda, Cecilia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina Fil: Cimino, Rubén Oscar. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Diosque, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina Fil: Basombrío, Miguel Ángel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina 2018-07-26T13:17:34Z 2018-07-26T13:17:34Z 2017 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/2884 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702110/ 1471-2334 10.1186/s12879-017-2834-6 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf BioMed Central BMC infectious diseases 17 : 732. (2017) |
| spellingShingle | Trypanosoma Cruzi Infección Experimental Respuesta Inmunológica Vectores Plásmidos Plasmid Vectors Immune Response Experimental Infection IFN-γ Plasmid pVXVR-mIFN-y Pérez Brandan, Cecilia María Mesías, Andrea Cecilia Parodi Ramoneda, Cecilia María Cimino, Rubén Oscar Perez Brandan, Carolina Diosque, Patricio Basombrío, Miguel Angel Manuel Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites |
| title | Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites |
| title_full | Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites |
| title_fullStr | Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites |
| title_full_unstemmed | Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites |
| title_short | Effects of IFN-γ coding plasmid supplementation in the immune response and protection elicited by Trypanosoma cruzi attenuated parasites |
| title_sort | effects of ifn γ coding plasmid supplementation in the immune response and protection elicited by trypanosoma cruzi attenuated parasites |
| topic | Trypanosoma Cruzi Infección Experimental Respuesta Inmunológica Vectores Plásmidos Plasmid Vectors Immune Response Experimental Infection IFN-γ Plasmid pVXVR-mIFN-y |
| url | http://hdl.handle.net/20.500.12123/2884 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702110/ |
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