Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFMA |
Texto Completo: | https://tedebc.ufma.br/jspui/handle/tede/tede/5050 |
Resumo: | Human schistosomiasis is a neglected parasitic disease of significant public health relevance caused by trematode helminths of the species Schistosoma mansoni. Macrophages play a crucial role during S. mansoni infection and can adopt different phenotypes. Despite the importance of macrophages in infection control, the involvement of functional macrophage types in schistosomiasis remains poorly defined. This study was divided into two chapters with the aim of expanding prospective investigations into macrophage polarization in schistosomiasis. In Chapter 1, we provide a brief review highlighting diverse pathways of molecule and/or macrophage activation and polarization during the disease. This review is based on original and review articles obtained from major databases, including Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS, and ScienceDirect. The results underscore the significance of S. mansoni and Schistosoma japonicum antigens in macrophage polarization, as they exert immunomodulatory effects at different disease stages. In Chapter 2, the objective was to assess macrophage responses in the presence of S. mansoni cercariae and adult worms in vitro, as well as the expression of M1 and M2 macrophage markers in hepatic tissue in a murine model of chronic S. mansoni infection. In vitro assays employed macrophages (RAW 264.7) cultured at a concentration of 1x106 /mL, including non- polarized (M0) macrophages, M1 macrophages previously polarized with LPS (2000 ng/mL) and IFN-γ (100 ng/mL), and M2 macrophages with IL-4 (400 ng/mL) and IL-13 (200 ng/mL). These cells were co-cultured with cercariae (10 cercariae/well) or adult worms (2 worms/well) of S. mansoni. After 24 hours and 72 hours, cercariae and adult worm viability, respectively, were assessed. Furthermore, we investigated whether adult worms could influence the polarization of previously activated macrophages by quantifying iNOS and Arginase expression, nitric oxide production, cytokine production, and Arginase activity. In in vivo studies, M1 and M2 macrophage expression in the hepatic tissue of mice infected with 50 cercariae of S. mansoni after 90 days of infection was evaluated, using uninfected mice as controls. The in vitro results revealed that both non-polarized (M0) and M1 macrophages displayed cytotoxicity against S. mansoni cercariae and adult worms. Interestingly, adult worms had the capacity to potentiate the polarization of previously stimulated macrophages, inducing an M1 profile in M0 macrophages. In vivo, there was a significant increase in the expression of specific markers associated with M1 and M2 profiles in the hepatic tissues of infected mice. Furthermore, we observed that M2 macrophage expression exceeded that of M1 macrophages in the hepatic tissue of these infected animals, and this predominance of M2 macrophages was correlated with a reduction in the number of hepatic granulomas. Importantly, our investigation revealed that neither M1 nor M2 macrophages significantly influenced liver weight or hepatic granuloma size. In summary, macrophages can adopt different profiles at each stage of S. mansoni infection, mitigating host damage while potentially enhancing parasite survival. These findings are valuable for the development of vaccines and immunotherapies against schistosomiasis, as they elucidate the mechanisms by which macrophages can contribute to infection protection or pathogenesis. |
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NASCIMENTO, Flávia Raquel Fernandeshttp://lattes.cnpq.br/9073277157401960MIRANDA, Guilherme Silvahttp://lattes.cnpq.br/3641712922639207NASCIMENTO, Flávia Raquel Fernandeshttp://lattes.cnpq.br/9073277157401960SOUZA, Valdenia Maria Oliveira dehttp://lattes.cnpq.br/8056939101932406NASCIMENTO, Johnny Ramos dohttp://lattes.cnpq.br/8835152858874648LUZ, Hermes Ribeirohttp://lattes.cnpq.br/9243136309857451CARVALHO, Rafael Cardosohttp://lattes.cnpq.br/3863794712744490http://lattes.cnpq.br/4479988227259248FONSECA, Irlla Correia Lima Licá2023-11-17T17:27:21Z2023-10-24FONSECA, Irlla Correia Lima Licá. Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907. 2023. 146 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2023.https://tedebc.ufma.br/jspui/handle/tede/tede/5050Human schistosomiasis is a neglected parasitic disease of significant public health relevance caused by trematode helminths of the species Schistosoma mansoni. Macrophages play a crucial role during S. mansoni infection and can adopt different phenotypes. Despite the importance of macrophages in infection control, the involvement of functional macrophage types in schistosomiasis remains poorly defined. This study was divided into two chapters with the aim of expanding prospective investigations into macrophage polarization in schistosomiasis. In Chapter 1, we provide a brief review highlighting diverse pathways of molecule and/or macrophage activation and polarization during the disease. This review is based on original and review articles obtained from major databases, including Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS, and ScienceDirect. The results underscore the significance of S. mansoni and Schistosoma japonicum antigens in macrophage polarization, as they exert immunomodulatory effects at different disease stages. In Chapter 2, the objective was to assess macrophage responses in the presence of S. mansoni cercariae and adult worms in vitro, as well as the expression of M1 and M2 macrophage markers in hepatic tissue in a murine model of chronic S. mansoni infection. In vitro assays employed macrophages (RAW 264.7) cultured at a concentration of 1x106 /mL, including non- polarized (M0) macrophages, M1 macrophages previously polarized with LPS (2000 ng/mL) and IFN-γ (100 ng/mL), and M2 macrophages with IL-4 (400 ng/mL) and IL-13 (200 ng/mL). These cells were co-cultured with cercariae (10 cercariae/well) or adult worms (2 worms/well) of S. mansoni. After 24 hours and 72 hours, cercariae and adult worm viability, respectively, were assessed. Furthermore, we investigated whether adult worms could influence the polarization of previously activated macrophages by quantifying iNOS and Arginase expression, nitric oxide production, cytokine production, and Arginase activity. In in vivo studies, M1 and M2 macrophage expression in the hepatic tissue of mice infected with 50 cercariae of S. mansoni after 90 days of infection was evaluated, using uninfected mice as controls. The in vitro results revealed that both non-polarized (M0) and M1 macrophages displayed cytotoxicity against S. mansoni cercariae and adult worms. Interestingly, adult worms had the capacity to potentiate the polarization of previously stimulated macrophages, inducing an M1 profile in M0 macrophages. In vivo, there was a significant increase in the expression of specific markers associated with M1 and M2 profiles in the hepatic tissues of infected mice. Furthermore, we observed that M2 macrophage expression exceeded that of M1 macrophages in the hepatic tissue of these infected animals, and this predominance of M2 macrophages was correlated with a reduction in the number of hepatic granulomas. Importantly, our investigation revealed that neither M1 nor M2 macrophages significantly influenced liver weight or hepatic granuloma size. In summary, macrophages can adopt different profiles at each stage of S. mansoni infection, mitigating host damage while potentially enhancing parasite survival. These findings are valuable for the development of vaccines and immunotherapies against schistosomiasis, as they elucidate the mechanisms by which macrophages can contribute to infection protection or pathogenesis.A esquistossomose humana é uma doença parasitária negligenciada de grande relevância para saúde pública, sendo causada por helmintos trematódeos da espécie Schistosoma mansoni. Durante a infecção por S. mansoni os macrófagos desempenham um papel crucial na proteção e na patogênese e podem adquirir diferentes fenótipos. Apesar da relevância dos macrófagos no controle de infecções, a participação dos tipos funcionais destas células na esquistossomose não é bem definida. Assim, o presente trabalho foi dividido em dois capítulos com intuito de ampliar estudos prospectivos sobre a polarização de macrófagos na esquistossomose. No capítulo 1, fornecemos uma breve revisão que destaca diferentes vias de ativação e polarização de moléculas e/ou macrófagos durante na respectiva doença. Esta revisão é baseada em artigos originais e de revisão obtidos por meio de buscas nas principais bases de dados, incluindo Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS e ScienceDirect. Os resultados demonstram a importância dos antígenos de S. mansoni e Schistosoma japonicum na polarização de macrófagos, pois exercem efeitos imunomoduladores em diferentes estágios da doença. No capítulo 2, foram avaliadas as respostas dos macrófagos na presença de cercárias e vermes adultos de S. mansoni in vitro, bem como a expressão dos marcadores para macrófagos M1 e M2 no tecido hepático em um modelo murino de infecção crônica por S. mansoni. Nos ensaios in vitro foram utilizados macrófagos (RAW 264.7) cultivados na concentração de 1x106 /mL não polarizados (M0). Também foram utilizados macrófagos M1 previamente polarizados com LPS (2000 ng/mL) e IFN-γ (100 ng/mL) e macrófagos M2 com IL-4 (400 ng/mL) e IL-13 (200 ng/mL). Essas células foram co-cultivadas com cercárias (10 cercárias/ poço) ou com vermes adultos (2 vermes/ poço) de S. Mansoni. Após 24 horas e 72 horas, avaliou-se a viabilidade das cercárias e vermes adultos, respectivamente. Em seguida, avaliou-se se vermes adultos poderiam interferir na polarização de macrófagos previamente ativados a partir da quantificação da expressão de iNOS e Arginase, da produção de óxido nítrico e de citocinas, além da atividade da Arginase. Nos estudos in vivo, foi avaliada expressão de macrófagos M1 e M2 no tecido de hepático de camundongos infectados com 50 cercárias de S. mansoni após 90 dias de infecção. Camundongos sem infecção, foram utilizados como controle. Os resultados in vitro, mostraram que macrófagos M0 e macrófagos M1 foram citotóxicos para as cercárias e vermes adultos de S. mansoni. Os vermes adultos foram capazes potencializar a polarização de macrófagos previamente estimulados, induzindo um perfil M1 em macrófagos M0. In vivo, houve um aumento significativo na expressão de marcadores específicos associados aos perfis M1 e M2 nos tecidos hepáticos de camundongos infectados. A expressão de macrófagos M2 foi maior que de macrófagos M1, e essa predominância de macrófagos M2 está correlacionada com a redução no número de granulomas hepáticos. Observou-se que os macrófagos M1 e M2 não exerceram influência no aumento do peso do fígado ou no tamanho dos granulomas hepáticos. Esses achados são importantes para o desenvolvimento de vacinas e imunoterapias contra a esquistossomose, pois revelam os mecanismos pelos quais os macrófagos podem contribuir para a proteção ou a patogênese da infecçãoSubmitted by Jonathan Sousa de Almeida (jonathan.sousa@ufma.br) on 2023-11-17T17:27:21Z No. of bitstreams: 1 IRLLACORREIALIMALICÁFONSÊCA.pdf: 4280002 bytes, checksum: dd0003bad4eb4f5e535e10dd007cb721 (MD5)Made available in DSpace on 2023-11-17T17:27:21Z (GMT). No. of bitstreams: 1 IRLLACORREIALIMALICÁFONSÊCA.pdf: 4280002 bytes, checksum: dd0003bad4eb4f5e535e10dd007cb721 (MD5) Previous issue date: 2023-10-24CAPESapplication/pdfporUniversidade Federal do MaranhãoPROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBSUFMABrasilDEPARTAMENTO DE PATOLOGIA/CCBSArginase;Cercárias;Citocinas;iNOS;Óxido nítrico;Schistosoma mansoni.Arginase;Cercariae;Cytokines;iNOS;Nitric oxide;Schistosoma mansoni.Ciências da SaúdeAvaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907Evaluation of macrophage polarization during infection by Schistosoma mansoni Sambon,1907info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFMAinstname:Universidade Federal do Maranhão (UFMA)instacron:UFMAORIGINALIRLLACORREIALIMALICÁFONSÊCA.pdfIRLLACORREIALIMALICÁFONSÊCA.pdfapplication/pdf4280002http://tedebc.ufma.br:8080/bitstream/tede/5050/2/IRLLACORREIALIMALIC%C3%81FONS%C3%8ACA.pdfdd0003bad4eb4f5e535e10dd007cb721MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82255http://tedebc.ufma.br:8080/bitstream/tede/5050/1/license.txt97eeade1fce43278e63fe063657f8083MD51tede/50502023-11-17 14:27:21.858oai:tede2: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Biblioteca Digital de Teses e Dissertaçõeshttps://tedebc.ufma.br/jspui/PUBhttp://tedebc.ufma.br:8080/oai/requestrepositorio@ufma.br||repositorio@ufma.bropendoar:21312023-11-17T17:27:21Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA)false |
dc.title.por.fl_str_mv |
Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907 |
dc.title.alternative.eng.fl_str_mv |
Evaluation of macrophage polarization during infection by Schistosoma mansoni Sambon,1907 |
title |
Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907 |
spellingShingle |
Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907 FONSECA, Irlla Correia Lima Licá Arginase; Cercárias; Citocinas; iNOS; Óxido nítrico; Schistosoma mansoni. Arginase; Cercariae; Cytokines; iNOS; Nitric oxide; Schistosoma mansoni. Ciências da Saúde |
title_short |
Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907 |
title_full |
Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907 |
title_fullStr |
Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907 |
title_full_unstemmed |
Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907 |
title_sort |
Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907 |
author |
FONSECA, Irlla Correia Lima Licá |
author_facet |
FONSECA, Irlla Correia Lima Licá |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
NASCIMENTO, Flávia Raquel Fernandes |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9073277157401960 |
dc.contributor.advisor-co1.fl_str_mv |
MIRANDA, Guilherme Silva |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/3641712922639207 |
dc.contributor.referee1.fl_str_mv |
NASCIMENTO, Flávia Raquel Fernandes |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/9073277157401960 |
dc.contributor.referee2.fl_str_mv |
SOUZA, Valdenia Maria Oliveira de |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/8056939101932406 |
dc.contributor.referee3.fl_str_mv |
NASCIMENTO, Johnny Ramos do |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/8835152858874648 |
dc.contributor.referee4.fl_str_mv |
LUZ, Hermes Ribeiro |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/9243136309857451 |
dc.contributor.referee5.fl_str_mv |
CARVALHO, Rafael Cardoso |
dc.contributor.referee5Lattes.fl_str_mv |
http://lattes.cnpq.br/3863794712744490 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4479988227259248 |
dc.contributor.author.fl_str_mv |
FONSECA, Irlla Correia Lima Licá |
contributor_str_mv |
NASCIMENTO, Flávia Raquel Fernandes MIRANDA, Guilherme Silva NASCIMENTO, Flávia Raquel Fernandes SOUZA, Valdenia Maria Oliveira de NASCIMENTO, Johnny Ramos do LUZ, Hermes Ribeiro CARVALHO, Rafael Cardoso |
dc.subject.por.fl_str_mv |
Arginase; Cercárias; Citocinas; iNOS; Óxido nítrico; Schistosoma mansoni. |
topic |
Arginase; Cercárias; Citocinas; iNOS; Óxido nítrico; Schistosoma mansoni. Arginase; Cercariae; Cytokines; iNOS; Nitric oxide; Schistosoma mansoni. Ciências da Saúde |
dc.subject.eng.fl_str_mv |
Arginase; Cercariae; Cytokines; iNOS; Nitric oxide; Schistosoma mansoni. |
dc.subject.cnpq.fl_str_mv |
Ciências da Saúde |
description |
Human schistosomiasis is a neglected parasitic disease of significant public health relevance caused by trematode helminths of the species Schistosoma mansoni. Macrophages play a crucial role during S. mansoni infection and can adopt different phenotypes. Despite the importance of macrophages in infection control, the involvement of functional macrophage types in schistosomiasis remains poorly defined. This study was divided into two chapters with the aim of expanding prospective investigations into macrophage polarization in schistosomiasis. In Chapter 1, we provide a brief review highlighting diverse pathways of molecule and/or macrophage activation and polarization during the disease. This review is based on original and review articles obtained from major databases, including Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS, and ScienceDirect. The results underscore the significance of S. mansoni and Schistosoma japonicum antigens in macrophage polarization, as they exert immunomodulatory effects at different disease stages. In Chapter 2, the objective was to assess macrophage responses in the presence of S. mansoni cercariae and adult worms in vitro, as well as the expression of M1 and M2 macrophage markers in hepatic tissue in a murine model of chronic S. mansoni infection. In vitro assays employed macrophages (RAW 264.7) cultured at a concentration of 1x106 /mL, including non- polarized (M0) macrophages, M1 macrophages previously polarized with LPS (2000 ng/mL) and IFN-γ (100 ng/mL), and M2 macrophages with IL-4 (400 ng/mL) and IL-13 (200 ng/mL). These cells were co-cultured with cercariae (10 cercariae/well) or adult worms (2 worms/well) of S. mansoni. After 24 hours and 72 hours, cercariae and adult worm viability, respectively, were assessed. Furthermore, we investigated whether adult worms could influence the polarization of previously activated macrophages by quantifying iNOS and Arginase expression, nitric oxide production, cytokine production, and Arginase activity. In in vivo studies, M1 and M2 macrophage expression in the hepatic tissue of mice infected with 50 cercariae of S. mansoni after 90 days of infection was evaluated, using uninfected mice as controls. The in vitro results revealed that both non-polarized (M0) and M1 macrophages displayed cytotoxicity against S. mansoni cercariae and adult worms. Interestingly, adult worms had the capacity to potentiate the polarization of previously stimulated macrophages, inducing an M1 profile in M0 macrophages. In vivo, there was a significant increase in the expression of specific markers associated with M1 and M2 profiles in the hepatic tissues of infected mice. Furthermore, we observed that M2 macrophage expression exceeded that of M1 macrophages in the hepatic tissue of these infected animals, and this predominance of M2 macrophages was correlated with a reduction in the number of hepatic granulomas. Importantly, our investigation revealed that neither M1 nor M2 macrophages significantly influenced liver weight or hepatic granuloma size. In summary, macrophages can adopt different profiles at each stage of S. mansoni infection, mitigating host damage while potentially enhancing parasite survival. These findings are valuable for the development of vaccines and immunotherapies against schistosomiasis, as they elucidate the mechanisms by which macrophages can contribute to infection protection or pathogenesis. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-11-17T17:27:21Z |
dc.date.issued.fl_str_mv |
2023-10-24 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
FONSECA, Irlla Correia Lima Licá. Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907. 2023. 146 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2023. |
dc.identifier.uri.fl_str_mv |
https://tedebc.ufma.br/jspui/handle/tede/tede/5050 |
identifier_str_mv |
FONSECA, Irlla Correia Lima Licá. Avaliação da polarização de macrófagos durante infecção por Schistosoma mansoni Sambon,1907. 2023. 146 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2023. |
url |
https://tedebc.ufma.br/jspui/handle/tede/tede/5050 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal do Maranhão |
dc.publisher.program.fl_str_mv |
PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBS |
dc.publisher.initials.fl_str_mv |
UFMA |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
DEPARTAMENTO DE PATOLOGIA/CCBS |
publisher.none.fl_str_mv |
Universidade Federal do Maranhão |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFMA instname:Universidade Federal do Maranhão (UFMA) instacron:UFMA |
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Universidade Federal do Maranhão (UFMA) |
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UFMA |
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UFMA |
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Biblioteca Digital de Teses e Dissertações da UFMA |
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Biblioteca Digital de Teses e Dissertações da UFMA |
bitstream.url.fl_str_mv |
http://tedebc.ufma.br:8080/bitstream/tede/5050/2/IRLLACORREIALIMALIC%C3%81FONS%C3%8ACA.pdf http://tedebc.ufma.br:8080/bitstream/tede/5050/1/license.txt |
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repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA) |
repository.mail.fl_str_mv |
repositorio@ufma.br||repositorio@ufma.br |
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1809926218081894400 |