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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Barral-netto, M. Reed, S. G. Brownell, C. E. Twardzik, D. R. Barral, A. Yong, E. C. |
| Description | Author Affiliation: Barral A ( Seattle Biomedical Research Institute, WA 98109.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 90 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1993-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Leishmania Braziliensis Pathogenicity Leishmaniasis, Cutaneous Immunology Macrophages Transforming Growth Factor Beta Physiology Virulence Actins Genetics Animals Interferon-gamma Interleukin-2 Interleukin-4 Growth & Development Physiopathology Drug Effects Parasitology Mice Mice, Inbred BALB C Molecular Sequence Data Oligodeoxyribonucleotides Polymerase Chain Reaction RNA Isolation & Purification Recombinant Proteins Pharmacology Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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