Alternative Th17 and CD4+CD25+FoxP3+ cell frequencies increase and correlate with worse cardiac function in Chagas cardiomyopathy

• Published in: Scandinavian journal of immunology 2018-04, Vol.87 (4), p.e12650-n/a
• Main Authors: Almeida, M. S., Lorena, V. M. B., Medeiros, C. de A., Junior, W. O., Cavalcanti, M. da G. A. M., Martins, S. M., de Morais, C. N. L.
• Format: Article
• Language: English
• Subjects: Antigens; Cardiomyopathy; CD25 antigen; CD4 antigen; Chagas; Chagas disease; Coronary artery disease; Flow cytometry; Fluorescence; Foxp3 protein; Heart diseases; Helper cells; Homeostasis; Immunoregulation; Interferon; interleukin 17; Lymphocytes B; Lymphocytes T; Peripheral blood; Th17; Treg; Vector-borne diseases
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/sji.12650

Immune homeostasis has been suggested to play an important role in the clinical evolution of chronic Chagas disease; however, the immunopathologic factors involved have not been fully elucidated. Therefore, our study aimed to analyse the frequency of CD4+CD25+FoxP3+ cells, classic Th17 cells, alternative Th17 cells and IL‐17+ B cells from peripheral blood of chronic cardiac patients after in vitro stimulation with Trypanosoma cruzi soluble EPI antigen. Patients were selected and classified according to clinical evaluation of cardiac involvement: mild, B1 (CARD1) (n = 20) and severe, C (CARD2) (n = 11). Patients with the indeterminate form of CD were included as the control group A (IND) (n = 17). Blood samples were collected and cultured in the presence of EPI antigen. Cells frequency and median fluorescence intensity (MFI) were obtained by flow cytometry. Our results showed that only CD4+CD25+FoxP3+, CD4+CD25highFoxP3+, CD4+IL‐17+IFN‐γ− and CD4+IL‐17+IFN‐γ+ cells are more frequent in patients with severe cardiac disease and correlate with worse global cardiac function. However, while indeterminate patients demonstrated a positive correlation between CD4+CD25+FoxP3+ and CD4+IL‐17+IFN‐γ− Th17 cells, this relationship was not observed in cardiac patients. IL‐17 expression by Th17 cells and B cells correlated with disease progression. Altogether our results suggest that the clinical progression of Chagas cardiomyopathy involves worsening of inflammation and impairment of immunoregulatory mechanisms.