Plasma Levels of sFas-sFasL and FASL Gene Expression Are Associated with Tuberculosis
Iury de Paula Souza1,2, Ednelza da Silva Graça Amoras1, Francisca Dayse Martins de Sousa1,2
1Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém 66075-110, Brazil.
Abstract:
Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is an important immune mechanism against infection. This study investigated the association of tuberculosis (TB) with the presence of the polymorphisms FAS -670A/G and FASL -124A/G, the levels of sFas and sFasL, and the gene expression of FASL and cytokines. Samples of 200 individuals diagnosed with TB and 200 healthy controls were evaluated. Real-time PCR (genotyping and gene expression) and ELISA (dosages of sFas, sFasL, IFN-γ, and IL-10) tests were performed. There was no association of FAS -670A/G and FASL -124A/G polymorphisms with TB. The TB group exhibited high plasma levels of sFas and reduced plasma levels of sFasL (p < 0.05). The correlation analysis between these markers revealed a positive correlation between the levels of sFas and sFasL, sFasL and FASL expression, and between sFas and FASL expression (p < 0.05). In the TB group, there was a positive correlation between FASL expression and IFN-γ levels and higher levels of IL-10 compared to IFN-γ (p < 0.05). High levels of sFas and reduced levels of sFasL and FASL expression may contribute to the inhibition of apoptosis in infected cells and represent a possible bacterial resistance resource to maintain the infection.
Insights
Tuberculosis (TB) infection is not linked to FAS or FASL gene polymorphisms. However, TB patients show higher soluble Fas (sFas) and lower soluble Fas ligand (sFasL) levels, potentially aiding bacterial survival.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is a key immune response.
- Understanding the genetic and molecular factors influencing this process is crucial for TB control.
Purpose of the Study:
- To investigate the association of FAS and FASL gene polymorphisms with tuberculosis (TB).
- To evaluate the levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) and gene expression of FASL in TB patients.
- To explore the correlation between these markers and cytokine levels (IFN-γ, IL-10) in TB.
Main Methods:
- Genotyping of FAS -670A/G and FASL -124A/G polymorphisms using real-time PCR.
- Quantification of sFas, sFasL, IFN-γ, and IL-10 using ELISA.
- Measurement of FASL gene expression via real-time PCR.
Main Results:
- No association was found between FAS/FASL polymorphisms and TB.
- TB patients exhibited significantly higher plasma sFas levels and lower sFasL levels compared to controls.
- Positive correlations were observed between sFas and sFasL levels, FASL expression, and between sFas and FASL expression.
Conclusions:
- Elevated sFas and reduced sFasL, along with decreased FASL expression, may impair macrophage apoptosis in TB patients.
- These alterations could represent a bacterial resistance mechanism, facilitating Mycobacterium tuberculosis persistence.
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