Immunosuppressive CD14+/HLA-DRlow/‒ monocytes in patients with Chagas Disease

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-DR^low/‒) 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-DR^low/‒ 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-DR^low/‒ 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-DR^low/- 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.

Keywords: Chagas disease; Immunoregulation; Myeloid-derived suppressor cells.