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Microscopy-based Assays for High-throughput Screening of Host Factors Involved in Brucella Infection of Hela Cells
Published on: August 5, 2016
Transforming growth factor beta production correlates with depressed lymphocytes function in humans with chronic
Mohamed G Elfaki1, Abdullah A Al-Hokail
1Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Takhassusi Road, PO Box 3354, MBC 03, Riyadh 11211, Saudi Arabia. elfaki@kfshrc.edu.sa
Insights
Transforming growth factor beta (TGF-beta) elevates in chronic brucellosis, suppressing T cell responses. Neutralizing TGF-beta restored immune function, suggesting a therapeutic target for this persistent infection.
Area of Science:
- Immunology
- Infectious Diseases
- Molecular Biology
Background:
- Chronic brucellosis involves immune dysregulation, with impaired cell-mediated immunity.
- The role of specific immunosuppressive factors in *Brucella melitensis* infection requires elucidation.
Purpose of the Study:
- To investigate the involvement of transforming growth factor beta (TGF-beta) in the immunosuppression observed in chronic brucellosis.
- To determine the relationship between TGF-beta levels and T cell dysfunction in patients with *Brucella melitensis* infection.
Main Methods:
- Quantification of circulating TGF-beta1 levels in patients and healthy controls.
- Measurement of TGF-beta1 production by peripheral blood mononuclear cells (PBMC) stimulated with *Brucella* cell extract (BCE).
- Assessment of TGF-beta mRNA expression and lymphoproliferative responses in patient PBMC.
- In vitro experiments using neutralizing antibodies to TGF-beta to restore lymphocyte function.
Main Results:
- Markedly elevated serum TGF-beta1 levels were found in patients with chronic brucellosis compared to controls.
- Stimulation with BCE antigen induced a 2-fold increase in TGF-beta1 production and mRNA expression in patient PBMC.
- Increased TGF-beta1 production correlated with diminished lymphoproliferative responses to BCE.
- Neutralization of TGF-beta1 restored the function of proliferating lymphocytes.
Conclusions:
- Elevated TGF-beta1 activity contributes to the depressed T cell function in chronic brucellosis.
- This TGF-beta1-mediated immunosuppression may lead to a prolonged disease course.
- Targeting TGF-beta1 presents a potential therapeutic strategy for managing chronic brucellosis.
Abstract:
In chronic brucellosis due to Brucella melitensis, cell-mediated responses were transiently depressed in comparison to antibody responses. To elucidate the mechanism of immunosuppression, we examined the role of transforming growth factor beta (TGF-beta) in cellular immune responses of 20 patients with chronic brucellosis. Circulating TGF-beta1 level was markedly elevated is sera of patients with confirmed brucellosis as compared with those from Brucella-negative healthy control subjects. In contrast, a 2-fold increase of TGF-beta1 production was demonstrated in patients peripheral blood mononuclear cells (PBMC)-stimulated with Brucella cell extract (BCE) antigen. The increased production of TGF-beta1 protein was dually associated with enhanced expression of TGF-beta mRNA in patients PBMC and diminished lymphoproliferative responses to BCE. A causal relationship between increased TGF-beta1 production and depressed lymphoproliferative responses was demonstrated by treatment of proliferating PBMC with a neutralizing antibody to TGF-beta1 where the lymphocytes function has been restored. These results suggest that the increased activity of TGF-beta1 may underlie the depressed function of T cell responses with consequent prolongation of disease course in patients with chronic brucellosis.