HGPRT and PNP: Recombinant Enzymes from <i>Schistosoma mansoni</i> and Their Role in Immunotherapy during Experimental Murine Schistosomiasis
Schistosomiasis is a parasitic infection caused by trematode worms (also called blood flukes) of the genus <i>Schistosoma</i> sp., which affects over 230 million people worldwide, causing 200,000 deaths annually. There is no vaccine or new drugs available, which represents a worrying asp...
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MDPI AG
2023-03-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/4/527 |
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| author | Bruna Dias de Lima Fragelli Ana Carolina Maragno Fattori Elisandra de Almeida Montija Joice Margareth de Almeida Rodolpho Cynthia Aparecida de Castro Krissia Franco de Godoy Camila Tita Nogueira Vanderlei Rodrigues Edson Garcia Soares Larissa Romanello Juliana R. Torini Humberto D’Muniz Pereira Fernanda de Freitas Anibal |
| author_facet | Bruna Dias de Lima Fragelli Ana Carolina Maragno Fattori Elisandra de Almeida Montija Joice Margareth de Almeida Rodolpho Cynthia Aparecida de Castro Krissia Franco de Godoy Camila Tita Nogueira Vanderlei Rodrigues Edson Garcia Soares Larissa Romanello Juliana R. Torini Humberto D’Muniz Pereira Fernanda de Freitas Anibal |
| author_sort | Bruna Dias de Lima Fragelli |
| collection | DOAJ |
| description | Schistosomiasis is a parasitic infection caused by trematode worms (also called blood flukes) of the genus <i>Schistosoma</i> sp., which affects over 230 million people worldwide, causing 200,000 deaths annually. There is no vaccine or new drugs available, which represents a worrying aspect, since there is loss of sensitivity of the parasite to the medication recommended by the World Health Organization, Praziquantel. The present study evaluated the effects of the recombinant enzymes of <i>S. mansoni</i> Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT), Purine Nucleoside Phosphorylase (PNP) and the MIX of both enzymes in the immunotherapy of schistosomiasis in murine model. These enzymes are part of the purine salvage pathway, the only metabolic pathway present in the parasite for this purpose, being essential for the synthesis of DNA and RNA. Female mice of Swiss and BALB/c strains were infected with cercariae and treated, intraperitoneally, with three doses of 100 µg of enzymes. After the immunotherapy, the eggs and adult worms were counted in the feces; the number of eosinophils from the fluid in the peritoneal cavity and peripheral blood was observed; and the quantification of the cytokine IL-4 and the production of antibodies IgE was analyzed. The evaluation of the number of granulomas and collagen deposition via histological slides of the liver was performed. The results demonstrate that immunotherapy with the enzyme HGPRT seems to stimulate the production of IL-4 and promoted a significant reduction of granulomas in the liver in treated animals. The treatment with the enzyme PNP and the MIX was able to reduce the number of worms in the liver and in the mesenteric vessels of the intestine, to reduce the number of eggs in the feces and to negatively modulate the number of eosinophils. Therefore, immunotherapy with the recombinant enzymes of <i>S. mansoni</i> HGPRT and PNP might contribute to the control and reduction of the pathophysiological aspects of schistosomiasis, helping to decrease the morbidity associated with the infection in murine model. |
| first_indexed | 2024-03-11T04:38:58Z |
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| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-11T04:38:58Z |
| publishDate | 2023-03-01 |
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| series | Pathogens |
| spelling | doaj.art-0dc9141efb994c3e8254f30cda9630da2023-11-17T20:47:59ZengMDPI AGPathogens2076-08172023-03-0112452710.3390/pathogens12040527HGPRT and PNP: Recombinant Enzymes from <i>Schistosoma mansoni</i> and Their Role in Immunotherapy during Experimental Murine SchistosomiasisBruna Dias de Lima Fragelli0Ana Carolina Maragno Fattori1Elisandra de Almeida Montija2Joice Margareth de Almeida Rodolpho3Cynthia Aparecida de Castro4Krissia Franco de Godoy5Camila Tita Nogueira6Vanderlei Rodrigues7Edson Garcia Soares8Larissa Romanello9Juliana R. Torini10Humberto D’Muniz Pereira11Fernanda de Freitas Anibal12Laboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, São Carlos 13565-905, BrazilLaboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, São Carlos 13565-905, BrazilLaboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, São Carlos 13565-905, BrazilLaboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, São Carlos 13565-905, BrazilLaboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, São Carlos 13565-905, BrazilLaboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, São Carlos 13565-905, BrazilDepartamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04039-032, BrazilDepartamento de Bioquímica e Imunologia, Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto 14040-900, BrazilLaboratório de Citopatologia, Departamento de Patologia e Medicina Legal, Universidade de São Paulo, Ribeirão Preto 14040-900, BrazilDepartamento de Saúde e Psicologia, Universidade do Estado de Minas Gerais, Unidade Ituiutaba, Ituiutaba 38302-192, BrazilLaboratório de Biologia Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13565-905, BrazilLaboratório de Biologia Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13565-905, BrazilLaboratório de Inflamação e Doenças Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, São Carlos 13565-905, BrazilSchistosomiasis is a parasitic infection caused by trematode worms (also called blood flukes) of the genus <i>Schistosoma</i> sp., which affects over 230 million people worldwide, causing 200,000 deaths annually. There is no vaccine or new drugs available, which represents a worrying aspect, since there is loss of sensitivity of the parasite to the medication recommended by the World Health Organization, Praziquantel. The present study evaluated the effects of the recombinant enzymes of <i>S. mansoni</i> Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT), Purine Nucleoside Phosphorylase (PNP) and the MIX of both enzymes in the immunotherapy of schistosomiasis in murine model. These enzymes are part of the purine salvage pathway, the only metabolic pathway present in the parasite for this purpose, being essential for the synthesis of DNA and RNA. Female mice of Swiss and BALB/c strains were infected with cercariae and treated, intraperitoneally, with three doses of 100 µg of enzymes. After the immunotherapy, the eggs and adult worms were counted in the feces; the number of eosinophils from the fluid in the peritoneal cavity and peripheral blood was observed; and the quantification of the cytokine IL-4 and the production of antibodies IgE was analyzed. The evaluation of the number of granulomas and collagen deposition via histological slides of the liver was performed. The results demonstrate that immunotherapy with the enzyme HGPRT seems to stimulate the production of IL-4 and promoted a significant reduction of granulomas in the liver in treated animals. The treatment with the enzyme PNP and the MIX was able to reduce the number of worms in the liver and in the mesenteric vessels of the intestine, to reduce the number of eggs in the feces and to negatively modulate the number of eosinophils. Therefore, immunotherapy with the recombinant enzymes of <i>S. mansoni</i> HGPRT and PNP might contribute to the control and reduction of the pathophysiological aspects of schistosomiasis, helping to decrease the morbidity associated with the infection in murine model.https://www.mdpi.com/2076-0817/12/4/527schistosomiasis<i>Schistosoma mansoni</i>immunotherapypurine salvage pathwayHGPRTPNP |
| spellingShingle | Bruna Dias de Lima Fragelli Ana Carolina Maragno Fattori Elisandra de Almeida Montija Joice Margareth de Almeida Rodolpho Cynthia Aparecida de Castro Krissia Franco de Godoy Camila Tita Nogueira Vanderlei Rodrigues Edson Garcia Soares Larissa Romanello Juliana R. Torini Humberto D’Muniz Pereira Fernanda de Freitas Anibal HGPRT and PNP: Recombinant Enzymes from <i>Schistosoma mansoni</i> and Their Role in Immunotherapy during Experimental Murine Schistosomiasis Pathogens schistosomiasis <i>Schistosoma mansoni</i> immunotherapy purine salvage pathway HGPRT PNP |
| title | HGPRT and PNP: Recombinant Enzymes from <i>Schistosoma mansoni</i> and Their Role in Immunotherapy during Experimental Murine Schistosomiasis |
| title_full | HGPRT and PNP: Recombinant Enzymes from <i>Schistosoma mansoni</i> and Their Role in Immunotherapy during Experimental Murine Schistosomiasis |
| title_fullStr | HGPRT and PNP: Recombinant Enzymes from <i>Schistosoma mansoni</i> and Their Role in Immunotherapy during Experimental Murine Schistosomiasis |
| title_full_unstemmed | HGPRT and PNP: Recombinant Enzymes from <i>Schistosoma mansoni</i> and Their Role in Immunotherapy during Experimental Murine Schistosomiasis |
| title_short | HGPRT and PNP: Recombinant Enzymes from <i>Schistosoma mansoni</i> and Their Role in Immunotherapy during Experimental Murine Schistosomiasis |
| title_sort | hgprt and pnp recombinant enzymes from i schistosoma mansoni i and their role in immunotherapy during experimental murine schistosomiasis |
| topic | schistosomiasis <i>Schistosoma mansoni</i> immunotherapy purine salvage pathway HGPRT PNP |
| url | https://www.mdpi.com/2076-0817/12/4/527 |
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