Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection
Trypanosoma cruzi, the aetiological agent of Chagas disease, has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (c-TXNPx), which catalyses the reduction to hydrogen peroxi...
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2018
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paper:paper_00192805_v155_n3_p367_Girard2023-06-08T14:40:17Z Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection B-cell epitope prediction chronic Chagas disease peroxiredoxin T-cell and B-cell response B lymphocyte antigen CD19 antigen CD4 antigen CD69 antigen CD8 antigen cytosolic tryparedoxin peroxidase gamma interferon granulocyte macrophage colony stimulating factor HLA DR antigen immunoglobulin G interleukin 10 peroxidase unclassified drug immunoglobulin G peroxidase protozoal protein protozoon antibody tryparedoxin peroxidase adaptive immunity adult antibody titer antigen expression Article asymptomatic infection cardiac patient cell proliferation cellular immunity Chagas disease clinical article comparative study controlled study cytokine release cytosol enzyme activity evaluation study female human human cell human tissue humoral immunity immunogenicity immunoglobulin blood level macrophage male priority journal adaptive immunity aged Chagas disease clinical trial immunology middle aged pathology Trypanosoma cruzi Adaptive Immunity Adult Aged Antibodies, Protozoan Chagas Disease Female Humans Immunoglobulin G Male Middle Aged Peroxidases Protozoan Proteins Trypanosoma cruzi Trypanosoma cruzi, the aetiological agent of Chagas disease, has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (c-TXNPx), which catalyses the reduction to hydrogen peroxide, small-chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its overexpression renders parasites more resistant to the oxidative defences of macrophages, favouring parasite survival. This work addressed the study of the specific humoral and cellular immune response triggered by c-TXNPx in human natural infection. Thus, sera and peripheral blood mononuclear cells (PBMC) were collected from chronically infected asymptomatic and cardiac patients, and non-infected individuals. Results showed that levels of IgG antibodies against c-TXNPx were low in sera from individuals across all groups. B-cell epitope prediction limited immunogenicity to a few, small regions on the c-TXNPx sequence. At a cellular level, PBMC from asymptomatic and cardiac patients proliferated and secreted interferon-γ after c-TXNPx stimulation, compared with mock control. However, only proliferation was higher in asymptomatic patients compared with cardiac and non-infected individuals. Furthermore, asymptomatic patients showed an enhanced frequency of CD19 + CD69 + cells upon exposure to c-TXNPx. Overall, our results show that c-TXNPx fails to induce a strong immune response in natural infection, being measurable only in those patients without any clinical symptoms. The low impact of c-TXNPx in the human immune response could be strategic for parasite survival, as it keeps this crucial antioxidant enzyme activity safe from the mechanisms of adaptive immune response. © 2018 John Wiley & Sons Ltd 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00192805_v155_n3_p367_Girard http://hdl.handle.net/20.500.12110/paper_00192805_v155_n3_p367_Girard |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
B-cell epitope prediction chronic Chagas disease peroxiredoxin T-cell and B-cell response B lymphocyte antigen CD19 antigen CD4 antigen CD69 antigen CD8 antigen cytosolic tryparedoxin peroxidase gamma interferon granulocyte macrophage colony stimulating factor HLA DR antigen immunoglobulin G interleukin 10 peroxidase unclassified drug immunoglobulin G peroxidase protozoal protein protozoon antibody tryparedoxin peroxidase adaptive immunity adult antibody titer antigen expression Article asymptomatic infection cardiac patient cell proliferation cellular immunity Chagas disease clinical article comparative study controlled study cytokine release cytosol enzyme activity evaluation study female human human cell human tissue humoral immunity immunogenicity immunoglobulin blood level macrophage male priority journal adaptive immunity aged Chagas disease clinical trial immunology middle aged pathology Trypanosoma cruzi Adaptive Immunity Adult Aged Antibodies, Protozoan Chagas Disease Female Humans Immunoglobulin G Male Middle Aged Peroxidases Protozoan Proteins Trypanosoma cruzi |
| spellingShingle |
B-cell epitope prediction chronic Chagas disease peroxiredoxin T-cell and B-cell response B lymphocyte antigen CD19 antigen CD4 antigen CD69 antigen CD8 antigen cytosolic tryparedoxin peroxidase gamma interferon granulocyte macrophage colony stimulating factor HLA DR antigen immunoglobulin G interleukin 10 peroxidase unclassified drug immunoglobulin G peroxidase protozoal protein protozoon antibody tryparedoxin peroxidase adaptive immunity adult antibody titer antigen expression Article asymptomatic infection cardiac patient cell proliferation cellular immunity Chagas disease clinical article comparative study controlled study cytokine release cytosol enzyme activity evaluation study female human human cell human tissue humoral immunity immunogenicity immunoglobulin blood level macrophage male priority journal adaptive immunity aged Chagas disease clinical trial immunology middle aged pathology Trypanosoma cruzi Adaptive Immunity Adult Aged Antibodies, Protozoan Chagas Disease Female Humans Immunoglobulin G Male Middle Aged Peroxidases Protozoan Proteins Trypanosoma cruzi Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection |
| topic_facet |
B-cell epitope prediction chronic Chagas disease peroxiredoxin T-cell and B-cell response B lymphocyte antigen CD19 antigen CD4 antigen CD69 antigen CD8 antigen cytosolic tryparedoxin peroxidase gamma interferon granulocyte macrophage colony stimulating factor HLA DR antigen immunoglobulin G interleukin 10 peroxidase unclassified drug immunoglobulin G peroxidase protozoal protein protozoon antibody tryparedoxin peroxidase adaptive immunity adult antibody titer antigen expression Article asymptomatic infection cardiac patient cell proliferation cellular immunity Chagas disease clinical article comparative study controlled study cytokine release cytosol enzyme activity evaluation study female human human cell human tissue humoral immunity immunogenicity immunoglobulin blood level macrophage male priority journal adaptive immunity aged Chagas disease clinical trial immunology middle aged pathology Trypanosoma cruzi Adaptive Immunity Adult Aged Antibodies, Protozoan Chagas Disease Female Humans Immunoglobulin G Male Middle Aged Peroxidases Protozoan Proteins Trypanosoma cruzi |
| description |
Trypanosoma cruzi, the aetiological agent of Chagas disease, has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (c-TXNPx), which catalyses the reduction to hydrogen peroxide, small-chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its overexpression renders parasites more resistant to the oxidative defences of macrophages, favouring parasite survival. This work addressed the study of the specific humoral and cellular immune response triggered by c-TXNPx in human natural infection. Thus, sera and peripheral blood mononuclear cells (PBMC) were collected from chronically infected asymptomatic and cardiac patients, and non-infected individuals. Results showed that levels of IgG antibodies against c-TXNPx were low in sera from individuals across all groups. B-cell epitope prediction limited immunogenicity to a few, small regions on the c-TXNPx sequence. At a cellular level, PBMC from asymptomatic and cardiac patients proliferated and secreted interferon-γ after c-TXNPx stimulation, compared with mock control. However, only proliferation was higher in asymptomatic patients compared with cardiac and non-infected individuals. Furthermore, asymptomatic patients showed an enhanced frequency of CD19 + CD69 + cells upon exposure to c-TXNPx. Overall, our results show that c-TXNPx fails to induce a strong immune response in natural infection, being measurable only in those patients without any clinical symptoms. The low impact of c-TXNPx in the human immune response could be strategic for parasite survival, as it keeps this crucial antioxidant enzyme activity safe from the mechanisms of adaptive immune response. © 2018 John Wiley & Sons Ltd |
| title |
Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection |
| title_short |
Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection |
| title_full |
Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection |
| title_fullStr |
Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection |
| title_full_unstemmed |
Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection |
| title_sort |
evaluation of the immune response against trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00192805_v155_n3_p367_Girard http://hdl.handle.net/20.500.12110/paper_00192805_v155_n3_p367_Girard |
| _version_ |
1768542970308460544 |