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Transforming growth factor-beta in human cutaneous leishmaniasis
1Faculdade de Medicina, Serviço de Imunologia, Universidade Federal da Bahia, Salvador-Bahia, Brazil.
The American Journal of Pathology
|October 1, 1995
Summary
Transforming growth factor-beta (TGF-beta) promotes parasite growth in human leishmaniasis by suppressing immune responses. This immune regulator is found in patient lesions, indicating its role in disease progression.
Area of Science:
- Immunology
- Parasitology
- Dermatology
Background:
- Transforming growth factor-beta (TGF-beta) is a potent immune-downregulatory cytokine.
- TGF-beta exacerbates disease in murine leishmaniasis models.
- Its role in human leishmaniasis remains to be fully elucidated.
Purpose of the Study:
- To investigate the involvement of TGF-beta in human leishmaniasis.
- To assess TGF-beta production by infected macrophages and its impact on parasite load.
- To examine TGF-beta expression in patient lesions.
Main Methods:
- Human macrophages were infected with Leishmania species (L. amazonensis, L. donovani chagasi, L. braziliensis).
- Active TGF-beta production was quantified.
- Exogenous TGF-beta and Interferon-gamma (IFN-γ) effects on parasite growth were evaluated.
- Tumor Necrosis Factor-alpha (TNF-α) effects were assessed.
- Immunohistochemistry was performed on patient biopsies.
Main Results:
- Human macrophages infected with Leishmania species produced active TGF-beta.
- Exogenous TGF-beta increased Leishmania parasite numbers in macrophages, counteracting IFN-γ.
- High concentrations of TNF-α blunted TGF-beta's suppressive effects.
- TGF-beta was detected in dermal fibroblasts and inflammatory cells in leishmaniasis lesions.
Conclusions:
- TGF-beta plays a significant role in human leishmaniasis pathogenesis.
- Macrophage-derived TGF-beta likely contributes to parasite establishment in early disease stages.
- TGF-beta may represent a therapeutic target for leishmaniasis.