Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7460
Title: Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis
Authors: Barral, Aldina Maria Prado
Barral Netto, Manoel
Yong, Elenita C.
Brownell, Cari E.
Twarzik, Daniel R.
Reed, Steven G
Affilliation: Seattle Biomedical Research Institute. Seattle, WA / Federal University of Bahia. Laboratory of Immunology. Salvador, BA, Brasil
Seattle Biomedical Research Institute. Seattle, WA / Federal University of Bahia. Laboratory of Immunology. Salvador, BA, Brasil
Seattle Biomedical Research Institute. Seattle, WA
Seattle Biomedical Research Institute. Seattle, WA
Bristol-Myers Squibb Pharmaceutical Research Institute. Seattle, WA
Cornell University Medical College. Division of International Medicine. Department of Medicine. New York, NY
Abstract: Transforming 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.
DeCS: Leishmania braziliensis/patogenicidade
Leishmaniose Cutânea/imunologia
Macrófagos/imunologia
Fator de Crescimento Transformador beta/fisiologia
Virulência/imunologia
Actinas/genética
Animais
Sequência de Bases
Humanos
Interferon gama/genética
Interleucina-2/genética
Leishmania braziliensis/crescimento & desenvolvimento
Macrófagos/efeitos de drogas
Camundongos
Camundongos Endogâmicos BALB C
Dados de Sequência Molecular
Oligodesoxirribonucleotídeos
Reação em Cadeia da Polimerase/métodos
Proteínas Recombinantes/farmacologia
RNA/genética
Issue Date: 1993
Publisher: Academy of Sciences of the USA
Citation: BARRAL, 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.
ISSN: 0027-8424
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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