This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barral, A. Articles by Barral-Netto, M. Search for Related Content PubMed PubMed Citation Articles by Barral, A. Articles by Barral-Netto, M.

American Journal of Pathology, Vol 147, 947-954, Copyright © 1995 by American Society for Investigative Pathology

REGULAR ARTICLES

Transforming growth factor-beta in human cutaneous leishmaniasis

A Barral, M Teixeira, P Reis, V Vinhas, J Costa, H Lessa, AL Bittencourt, S Reed, EM Carvalho and M Barral-Netto
Faculdade de Medicina, Servico de Imunologia, Universidade Federal da Bahia, Salvador-Bahia, Brazil.

Transforming growth factor (TGF)-beta has several downregulatory functions on the immune system: inhibition of interleukin-2 receptor induction, decrease of interferon-gamma-induced class II antigen expression, inhibition of macrophage activation, as well as cytotoxic and lymphokine-activated killer cell generation. TGF-beta has also been recognized as an important immunoregulator in murine leishmaniasis, for which it increases susceptibility to disease. In the present study we evaluate the involvement of TGF-beta in human leishmaniasis in vitro and in patients with cutaneous leishmaniasis. Human macrophages produce active TGF-beta after infection by Leishmania amazonensis (480 +/- 44.7 pg/ml; mean +/- SEM), L. donovani chagasi (295 +/- 7.6 pg/ml), or L. braziliensis (196 +/- 15.7 pg/ml). When TGF-beta was added to cultures of human macrophages infected with L. braziliensis it led to an increase of approximately 50% in parasite numbers as compared with untreated cultures. Exogenous TGF-beta added to macrophage cultures was able to reverse the effect of interferon-gamma in controlling Leishmania growth. Even at 100 IU/ml interferon-gamma the presence of TGF-beta increases the number of intracellular parasites. On the other hand, TNF-alpha at high concentration (100 IU/ml) totally blunts the suppressive effect of TGF-beta. Immunostaining for TGF-beta was observed in the dermis, produced by fibroblasts and occasionally by inflammatory cells in the biopsies from human leishmaniasis lesions, being present in most of the biopsies taken from patients with early cutaneous leishmaniasis (less than 2 months of ulcer development) and in cases of active mucosal leishmaniasis. Taken together these observations suggest an important role for TGF-beta in human leishmaniasis, with its production by infected macrophages being probably related to parasite establishment in the early stages of the disease.

This article has been cited by other articles:

				R. Khouri, A. Bafica, M. d. P. P. Silva, A. Noronha, J.-P. Kolb, J. Wietzerbin, A. Barral, M. Barral-Netto, and J. Van Weyenbergh IFN-{beta} Impairs Superoxide-Dependent Parasite Killing in Human Macrophages: Evidence for a Deleterious Role of SOD1 in Cutaneous Leishmaniasis J. Immunol., February 15, 2009; 182(4): 2525 - 2531. [Abstract] [Full Text] [PDF]

				L. Afonso, V. M. Borges, H. Cruz, F. L. Ribeiro-Gomes, G. A. DosReis, A. N. Dutra, J. Clarencio, C. I. de Oliveira, A. Barral, M. Barral-Netto, et al. Interactions with apoptotic but not with necrotic neutrophils increase parasite burden in human macrophages infected with Leishmania amazonensis J. Leukoc. Biol., August 1, 2008; 84(2): 389 - 396. [Abstract] [Full Text] [PDF]

				C. H. Serezani, J. H. Perrela, M. Russo, M. Peters-Golden, and S. Jancar Leukotrienes Are Essential for the Control of Leishmania amazonensis Infection and Contribute to Strain Variation in Susceptibility. J. Immunol., September 1, 2006; 177(5): 3201 - 3208. [Abstract] [Full Text] [PDF]

				G. Soares, A. Barral, J. M. Costa, M. Barral-Netto, and J. Van Weyenbergh CD16+ monocytes in human cutaneous leishmaniasis: increased ex vivo levels and correlation with clinical data J. Leukoc. Biol., January 1, 2006; 79(1): 36 - 39. [Abstract] [Full Text] [PDF]

				A. Kariminia, E. Bourreau, H. Pascalis, P. Couppie, D. Sainte-Marie, F. Tacchini-Cottier, and P. Launois Transforming Growth Factor {beta}1 Production by CD4+ CD25+ Regulatory T Cells in Peripheral Blood Mononuclear Cells from Healthy Subjects Stimulated with Leishmania guyanensis Infect. Immun., September 1, 2005; 73(9): 5908 - 5914. [Abstract] [Full Text] [PDF]

				L. U. Buxbaum, H. Denise, G. H. Coombs, J. Alexander, J. C. Mottram, and P. Scott Cysteine Protease B of Leishmania mexicana Inhibits Host Th1 Responses and Protective Immunity J. Immunol., October 1, 2003; 171(7): 3711 - 3717. [Abstract] [Full Text] [PDF]

				H. Renz and U. Herz The bidirectional capacity of bacterial antigens to modulate allergy and asthma Eur. Respir. J., January 1, 2002; 19(1): 158 - 171. [Abstract] [Full Text] [PDF]

				J Alexander, A. Satoskar, and D. Russell Leishmania species: models of intracellular parasitism J. Cell Sci., January 9, 1999; 112(18): 2993 - 3002. [Abstract] [PDF]

				S. Juttner, J. Bernhagen, C. N. Metz, M. Rollinghoff, R. Bucala, and A. Gessner Migration Inhibitory Factor Induces Killing of Leishmania major by Macrophages: Dependence on Reactive Nitrogen Intermediates and Endogenous TNF-{alpha} J. Immunol., September 1, 1998; 161(5): 2383 - 2390. [Abstract] [Full Text] [PDF]