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Immunosuppressive CD14+/HLA-DRlow/‒ monocytes in patients with Chagas Disease
Carlos Eduardo Menezes Viana1, Daniel Mazza Matos1, Maria de Fátima Oliveira2
1Department of Pathology and Legal Medicine of the Federal University of Ceará, Fortaleza, Brasil.
Insights
Chagas Disease (CD) progression may be linked to specific immune cells. Asymptomatic CD patients show more CD14+ myeloid-derived suppressor cells (MDSCs) with lower HLA-DR expression, potentially preventing disease worsening.
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- Chagas Disease (CD) pathogenesis remains unclear, particularly the transition from asymptomatic to symptomatic forms.
- Myeloid-derived suppressor cells (MDSCs), specifically CD14+ monocytes with low HLA-DR expression (CD14+/HLA-DRlow/–), regulate inflammation.
- The role of these MDSCs in CD progression is under investigation.
Purpose of the Study:
- To investigate the absolute number and HLA-DR expression of CD14+/HLA-DRlow/– monocytes in Chagas Disease patients.
- To compare these MDSC characteristics between asymptomatic (indeterminate) and symptomatic (cardiac, digestive, mixed) CD forms.
Main Methods:
- Flow cytometry was used to analyze peripheral blood samples.
- The study included 57 Chagas Disease patients: 23 asymptomatic and 34 symptomatic (26 cardiac, 8 mixed).
- Quantification of CD14+/HLA-DRlow/– monocytes and assessment of HLA-DR antigenic density were performed.
Main Results:
- Asymptomatic CD patients exhibited a significantly higher absolute number of CD14+/HLA-DRlow/– monocytes compared to symptomatic patients.
- A lower HLA-DR antigenic density was observed on these monocytes in the asymptomatic group.
- These findings suggest a distinct immune cell profile in the indeterminate phase of Chagas Disease.
Conclusions:
- The increased prevalence and altered phenotype of CD14+/HLA-DRlow/– monocytes in asymptomatic CD may contribute to immune suppression.
- This immune modulation could play a role in preventing or delaying the progression from indeterminate to symptomatic Chagas Disease.
- Further research is warranted to confirm the specific mechanisms and therapeutic potential.
Abstract:
Chagas Disease (CD) is a neglected illness whose immunopathological mechanisms have not yet been plainly elucidated. The asymptomatic (indeterminate) form of CD is a long-term condition and approximately 20% to 35% of the individuals with this form evolve into one of the three chronic symptomatic clinical forms of CD, namely: cardiac, digestive or cardio-digestive (mixed). A variant of blood monocytes characterized by low expression of the HLA-DR antigen (CD14+/HLA-DRlow/‒) constitutes a subtype of myeloid-derived suppressor cells (MDSCs) whose main function is to regulate exacerbated inflammatory processes. The development of the symptomatic forms of CD can be related to the interaction between the host's immune system and the CD14+/HLA-DRlow/‒ immunosuppressive monocytes. Here, we evaluated, by flow cytometry, the absolute number and the HLA-DR antigenic density of this population of MDSCs in 57 patients with the diagnosis of CD: 34 with the symptomatic clinical forms (26 cardiac and 8 mixed) and 23 with the asymptomatic (indeterminate) form. The asymptomatic form exhibited a greater number of CD14+/HLA-DRlow/‒ monocytes and, accordingly, a low HLA-DR antigenic density, when compared to the symptomatic forms. It is possible to speculate that the predominance of CD14+/HLA-DRlow/- monocytes in the patients with the asymptomatic (indeterminate) form might have been a factor that could delay or even prevent the evolution of the asymptomatic form to the symptomatic forms of Chagas Disease.
