Altered frequency of CD24highCD38high transitional B cells in patients with cardiac involvement of chronic Chagas disease.

Abstract

The cardiomyopathy developed by patients with chronic Chagas disease (CCD), one ofthe most severe consequences of T. cruzi infection, is mainly associated with animbalance between an excessive inflammatory reaction and a defectiveimmunomodulatory profile cause by host-parasite interaction. Despite the growingimportance of the regulatory function of B-cells in many malignancies, few studies haveaddressed their immunosuppressive role in chronic Chagas disease. In this work, wetackled this issue by studying the proportion of different B cell subpopulations and theircapacity to secrete IL-10 in individuals with distinct clinical forms of CCD. Seven-colourflow cytometry was performed to examine the peripheral blood B cell compartment inchronic Chagas disease (CCD) patients with and without cardiac manifestations (n=10 foreach 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 expressionof markers CD19, CD24 and CD38, we showed an expansion of total B cell andtransitional CD24highCD38high B cell subsets in CCD patients with cardiac involvementcompared to non-infected donors. Furthermore, although no differences were observed inthe frequency of total IL-10 producing B cells (B10) among the groups, CCD patients withcardiac involvement showed a statistically significant increased proportion of naïve B10cells and a tendency to an increased frequency of transitional B10 cells compared to noninfected donors. These findings suggest that immature transitional CD24highCD38high Bcells are greatly expanded in patients with the cardiac form of chronic Chagas disease andthese 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 cellsfollowed the same pattern in chronic patients without cardiac involvement and non-infectedindividuals. Our work provides insight into the phenotypic distribution of regulatory B cell inCCD, an important step towards new strategies to prevent cardiomiopathy associated withT. cruzi infection