Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis

dc.creatorBarral, Aldina Maria Prado
dc.creatorBarral Netto, Manoel
dc.creatorYong, Elenita C.
dc.creatorBrownell, Cari E.
dc.creatorTwarzik, Daniel R.
dc.creatorReed, Steven G
dc.date2014-03-27T13:29:23Z
dc.date2014-03-27T13:29:23Z
dc.date1993
dc.date.accessioned2023-09-26T20:56:23Z
dc.date.available2023-09-26T20:56:23Z
dc.identifierBARRAL, A. et al. Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis. Proceedings of the National Academy of Sciences of the USA, v. 90, p. 3442-3446, 1993.
dc.identifier0027-8424
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/7460
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8866499
dc.descriptionTransforming growth factor beta (TGF-beta) has potent down-regulating effects on macrophages and is thus capable of influencing the fate of intramacrophage parasites, including leishmanias. We report the development of a mouse model for the study of the human pathogen Leishmania braziliensis and demonstrate, both in vitro and in vivo, a key regulatory role for TGF-beta in the pathogenesis of infection with this parasite. Recombinant TGF-beta added to cultures of murine peritoneal macrophages led to increased intracellular L. braziliensis replication, whereas addition of neutralizing anti-TGF-beta monoclonal antibody decreased levels of infection. Macrophages infected with L. braziliensis produced biologically active TGF-beta, with a direct correlation between amounts of TGF-beta induced by two parasite isolates and their relative virulence. In vivo, treatment with recombinant TGF-beta rendered avirulent parasites virulent and activated latent L. braziliensis infection. Activation of parasite replication was observed in mice which had been infected with L. braziliensis 15 weeks previously but had not developed lesions or had healed lesions, depending on the parasite isolate used to infect the mice. The exacerbation of L. braziliensis infection in vivo was associated with an increase of interleukin 10 mRNA in the draining lymph node. These results demonstrate that TGF-beta is able to alter the course of in vitro and in vivo infections with L. braziliensis, the latter being characterized by an increase in interleukin 10, an important Th2 helper-T-cell cytokine.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAcademy of Sciences of the USA
dc.rightsopen access
dc.subjectLeishmania braziliensis/patogenicidade
dc.subjectLeishmaniose Cutânea/imunologia
dc.subjectMacrófagos/imunologia
dc.subjectFator de Crescimento Transformador beta/fisiologia
dc.subjectVirulência/imunologia
dc.subjectActinas/genética
dc.subjectAnimais
dc.subjectSequência de Bases
dc.subjectHumanos
dc.subjectInterferon gama/genética
dc.subjectInterleucina-2/genética
dc.subjectLeishmania braziliensis/crescimento & desenvolvimento
dc.subjectMacrófagos/efeitos de drogas
dc.subjectCamundongos
dc.subjectCamundongos Endogâmicos BALB C
dc.subjectDados de Sequência Molecular
dc.subjectOligodesoxirribonucleotídeos
dc.subjectReação em Cadeia da Polimerase/métodos
dc.subjectProteínas Recombinantes/farmacologia
dc.subjectRNA/genética
dc.titleTransforming growth factor beta as a virulence mechanism for Leishmania braziliensis
dc.typeArticle


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