{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:54:28Z","timestamp":1775073268449,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brazil (CAPES)","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Schistosomiasis is a parasitic infection caused by trematode worms (also called blood flukes) of the genus Schistosoma 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 S. mansoni 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 \u00b5g 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 S. mansoni 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.<\/jats:p>","DOI":"10.3390\/pathogens12040527","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T02:03:53Z","timestamp":1680055433000},"page":"527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HGPRT and PNP: Recombinant Enzymes from Schistosoma mansoni and Their Role in Immunotherapy during Experimental Murine Schistosomiasis"],"prefix":"10.3390","volume":"12","author":[{"given":"Bruna Dias","family":"de Lima Fragelli","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o e Doen\u00e7as Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4868-9148","authenticated-orcid":false,"given":"Ana Carolina Maragno","family":"Fattori","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o e Doen\u00e7as Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisandra","family":"de Almeida Montija","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o e Doen\u00e7as Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joice Margareth","family":"de Almeida Rodolpho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o e Doen\u00e7as Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia Aparecida","family":"de Castro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o e Doen\u00e7as Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krissia Franco","family":"de Godoy","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o e Doen\u00e7as Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Tita","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04039-032, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanderlei","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina, Universidade de S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edson Garcia","family":"Soares","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Citopatologia, Departamento de Patologia e Medicina Legal, Universidade de S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa","family":"Romanello","sequence":"additional","affiliation":[{"name":"Departamento de Sa\u00fade e Psicologia, Universidade do Estado de Minas Gerais, Unidade Ituiutaba, Ituiutaba 38302-192, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana R.","family":"Torini","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Estrutural, Instituto de F\u00edsica de S\u00e3o Carlos, Universidade de S\u00e3o Paulo, S\u00e3o Carlos 13565-905, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humberto D\u2019Muniz","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Estrutural, Instituto de F\u00edsica de S\u00e3o Carlos, Universidade de S\u00e3o Paulo, S\u00e3o Carlos 13565-905, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"de Freitas Anibal","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Inflama\u00e7\u00e3o e Doen\u00e7as Infecciosas, Departamento de Morfologia e Patologia, Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905, 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(2017). Field Use of Molluscicides in Schistosomiasis Control Programmes, World Health Organization (WHO)."},{"key":"ref_4","unstructured":"(2023, January 10). World Health Organization (WHO) Schistosomiasis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/schistosomiasis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.cbpa.2007.05.031","article-title":"Chemotherapy of Schistosomiasis: Present and Future","volume":"11","author":"Caffrey","year":"2007","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/01.qco.0000247591.13671.6a","article-title":"Schistosomiasis: Challenges for Control, Treatment and Drug Resistance","volume":"19","author":"Fenwick","year":"2006","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.actatropica.2015.04.016","article-title":"Schistosomiasis in Egypt: A Never-Ending Story?","volume":"148","author":"Othman","year":"2015","journal-title":"Acta Trop."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0166-6851(84)90062-8","article-title":"Purine Salvage in Schistosoma Mansoni Schistosomules","volume":"11","author":"Dovey","year":"1984","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0006-2952(73)90287-6","article-title":"Incorporation of Adenosine Analogs in vitro","volume":"22","author":"Stegman","year":"1973","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/0006-2952(77)90158-7","article-title":"Pathways of Nucleotide Metabolism in Schistosoma Mansoni\u2014VII","volume":"26","author":"Senft","year":"1977","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Torini, J.R., Romanello, L., Batista, F.A.H., Serr\u00e3o, V.H.B., Faheem, M., Zeraik, A.E., Bird, L., Nettleship, J., Reddivari, Y., and Owens, R. (2018). The Molecular Structure of Schistosoma Mansoni PNP Isoform 2 Provides Insights into the Nucleotide Selectivity of PNPs. PLoS ONE, 13.","DOI":"10.1101\/300533"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1021\/bi9616007","article-title":"Kinetic Mechanism of Human Hypoxanthine-Guanine Phosphoribosyltransferase: Rapid Phosphoribosyl Transfer Chemistry","volume":"36","author":"Xu","year":"1997","journal-title":"Biochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0163-7258(83)90031-1","article-title":"Purine Metabolism in the Schistosomes: Potential Targets for Chemotherapy","volume":"20","author":"Senft","year":"1983","journal-title":"Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/S0021-9258(17)36188-4","article-title":"Purification and Characterization of Hypoxanthine-Guanine Phosphoribosyltransferase from Schistosoma Mansoni. A Potential Target for Chemotherapy","volume":"261","author":"Dovey","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.molbiopara.2019.02.005","article-title":"In Vitro and in Vivo Characterization of the Multiple Isoforms of Schistosoma Mansoni Hypoxanthine-Guanine Phosphoribosyltransferases","volume":"229","author":"Romanello","year":"2019","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Fattori, A.C.M., Montija, E.d.A., Fragelli, B.D.d.L., Correia, R.D.O., de Castro, C.A., Romanello, L., Nogueira, C.T., Allegretti, S.M., Soares, E.G., and Pereira, H.D. (2023). Effects of Immunization with Recombinant Schistosoma Mansoni Enzymes AK and HGPRT: Murine Infection Control. Pathogens, 12.","DOI":"10.3390\/pathogens12010069"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"569988","DOI":"10.3389\/fimmu.2020.569988","article-title":"Investigating Immunization With Nucleotide Enzymes of Schistosoma Mansoni: Nucleoside Diphosphate Kinase and Adenylosuccinate Lyase as New Antigenic Targets Against Schistosomiasis","volume":"11","author":"Cagnazzo","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_18","first-page":"589","article-title":"Tecnica de Perfus\u0101o Para Colheita de Schistosoma Mansoni Em Cobaias Experimentalmente Infestadas","volume":"8","author":"Pellegrino","year":"1956","journal-title":"Ver. Bras. Malariol. D Trop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1007\/BF00931515","article-title":"Experimental Chemotherapy of Schistosoma Mansoni with Praziquantel and Oxamniquine: Differential Effect of Single or Combined Formulations of Drugs on Various Strains and on Both Sexes of the Parasite","volume":"78","author":"Delgado","year":"1992","journal-title":"Parasitol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1590\/S0074-02761998000700013","article-title":"Schistosomiasis Vaccine Development: Progress and Prospects","volume":"93","author":"Bergquist","year":"1998","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.ijpara.2004.05.001","article-title":"Determination of ED50 Values for Praziquantel in Praziquantel-Resistant and -Susceptible Schistosoma Mansoni Isolates","volume":"34","author":"Cioli","year":"2004","journal-title":"Int. J. Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e327","DOI":"10.1016\/S1473-3099(22)00221-3","article-title":"Review of 2022 WHO Guidelines on the Control and Elimination of Schistosomiasis","volume":"22","author":"Lo","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101341","DOI":"10.1016\/j.cimid.2019.101341","article-title":"Biological and Proteomic Studies of Schistosoma Mansoni with Decreased Sensitivity to Praziquantel","volume":"66","author":"Amer","year":"2019","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_24","first-page":"54","article-title":"Ant\u00edgenos Vacinais Contra Esquistossomose Mans\u00f4nica: Passado e Presente","volume":"6","author":"Rofatto","year":"2011","journal-title":"Biologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nri843","article-title":"The Immunobiology of Schistosomiasis","volume":"2","author":"Pearce","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_26","first-page":"49","article-title":"Immunization with Purine Salvation Pathway Recombinant Enzymes Induces the Production of Anti- Schistosoma Mansoni Immunoglobulines","volume":"1","author":"Neris","year":"2013","journal-title":"Int. Trends Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15069","DOI":"10.1038\/srep15069","article-title":"Lysosome-Associated Membrane Glycoprotein (LAMP)-Preliminary Study on a Hidden Antigen Target for Vaccination against Schistosomiasis","volume":"5","author":"Nawaratna","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.exppara.2009.04.006","article-title":"Schistosoma Mansoni: Effect of Dietary Zinc Supplement on Egg Granuloma in Swiss Mice Treated with Praziqantel","volume":"122","author":"Helmy","year":"2009","journal-title":"Exp. Parasitol."},{"key":"ref_29","first-page":"38","article-title":"Esquistossomose, Xistosa, Barriga d\u2019\u00e1gua","volume":"55","author":"Katz","year":"2016","journal-title":"Ci\u00eancia E Cult."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1016\/j.vaccine.2016.03.079","article-title":"Advancing a Vaccine to Prevent Human Schistosomiasis","volume":"34","author":"Merrifield","year":"2016","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5931","DOI":"10.1128\/IAI.72.10.5931-5937.2004","article-title":"Sm14 of Schistosoma Mansoni in Fusion with Tetanus Toxin Fragment C Induces Immunoprotection against Tetanus and Schistosomiasis in Mice","volume":"72","author":"Abreu","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fonseca, C.T., Braz Figueiredo Carvalho, G., Carvalho Alves, C., and De Melo, T.T. (2012). Schistosoma Tegument Proteins in Vaccine and Diagnosis Development: An Update. J. Parasitol. Res., 2012.","DOI":"10.1155\/2012\/541268"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Carvalho, O.S., Coelho, P.M.Z., and Lenzi, H.L. (2008). Organ. Schistosoma Mansoni Esquistossomose Uma Vis\u00e3o Multidiscip, Editora Fiocruz.","DOI":"10.7476\/9788575413708"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.molbiopara.2017.04.004","article-title":"Schistosoma Mansoni Displays an Adenine Phosphoribosyltransferase Preferentially Expressed in Mature Female Gonads and Vitelaria","volume":"214","author":"Zeraik","year":"2017","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/pim.12336","article-title":"Human Eosinophils Modulate Peripheral Blood Mononuclear Cell Response to Schistosoma Mansoni Adult Worm Antigen in Vitro","volume":"38","author":"Tweyongyere","year":"2016","journal-title":"Parasite Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/MOG.0b013e32835ab29a","article-title":"Eosinophils in Infection and Intestinal Immunity","volume":"29","author":"Hogan","year":"2013","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1182\/blood-2006-04-015933","article-title":"Schistosoma Mansoni Infection in Eosinophil Lineage-Ablated Mice","volume":"108","author":"Swartz","year":"2006","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1126\/science.8009216","article-title":"Immunoglobulin E and Effector Cells in Schistosomiasis","volume":"264","author":"Capron","year":"1994","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"22111","DOI":"10.1074\/jbc.M115.675066","article-title":"A Crystallin Fold in the Interleukin-4-Inducing Principle of Schistosoma Mansoni Eggs (IPSE\/\u03b1-1) Mediates IgE Binding for Antigen-Independent Basophil Activation","volume":"290","author":"Meyer","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/pim.12087","article-title":"Immunology of Human Schistosomiasis","volume":"36","author":"Colley","year":"2014","journal-title":"Parasite Immunol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/4\/527\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:05:31Z","timestamp":1760123131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/4\/527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,29]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["pathogens12040527"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12040527","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,29]]}}}