Altered frequency of CD24^highCD38^high transitional B cells in patients with cardiac involvement of chronic Chagas disease

Abstract

The cardiomyopathy developed by patients with chronic Chagas disease (CCD), one of the most severe consequences of T. cruzi infection, is mainly associated with an imbalance between an excessive inflammatory reaction and a defective immunomodulatory profile cause by host-parasite interaction. Despite the growing importance of the regulatory function of B-cells in many malignancies, few studies have addressed their immunosuppressive role in chronic Chagas disease. In this work, we tackled this issue by studying the proportion of different B cell subpopulations and their capacity to secrete IL-10 in individuals with distinct clinical forms of CCD. Seven-colour flow cytometry was performed to examine the peripheral blood B cell compartment in chronic Chagas disease (CCD) patients with and without cardiac manifestations (n=10 for each group) and non-infected donors (n=9). Peripheral blood mononuclear cells (PBMC)were incubated for 5h with PMA, ionomicyn and brefeldin A. According to the expression of markers CD24, CD38 and CD27 showed an expansion of total B cell and transitional CD24 high CD38 high B cell subsets in CCD patients and non-infected donors. Furthermore, although no differences were observed in the frequency of total IL-10 producing B cells (B10) among the groups, CCD patients with cardiac involvement showed an increased proportion of transitional and naïve B10 cells compared to non-infected donors. These findings suggest that immature transitional CD24 high CD38 high B cells are greatly expanded in patients with the cardiac form of chronic Chagas disease and these cells retain their ability to secrete IL-10 compared to non-infected donors. Furthermore, the distribution of naïve, transitional and memory B cells inside the B10 cells followed the same pattern in chronic patients without cardiac involvement and non-infected individuals. Our work provides insight into the phenotypic distribution of regulatory B cell in CCD, an important step towards new strategies to prevent cardiomiopathy associated with T. cruzi infection.

Host‐parasite dynamics in Chagas disease from systemic to hyper‐local scales

“…CD11b + B1 B cells from asymptomatic, infected individuals show increased capacity to produce IL‐10 compared to those with cardiac disease symptoms 138 . In addition, recent data show that when compared to non‐infected donors, chronically T. cruzi ‐infected individuals with cardiac manifestations have an increased proportion of immature transitional CD24 high CD38 high and naïve B cells able to produce IL‐10 upon in vitro re‐stimulation 160 . This suggests B cell–intrinsic IL‐10 signalling might be important to regulate the intense adaptive immune response, as is the case for other parasitic infections, 161 but direct mechanistic evidence is required to support this hypothesis.…”