Ex vivo characterization of Breg cells in patients with chronic Chagas disease

Magalí C Girard,Marisa Fernández,Gonzalo R Acevedo,Karina A Gómez,Raúl Chadi,Micaela S Ossowski,Yolanda Hernández

doi:10.1038/s41598-021-84765-x

Abstract

Despite the growing importance of the regulatory function of B cells in many infectious diseases, their immunosuppressive role remains elusive in chronic Chagas disease (CCD). Here, we studied the proportion of different B cell subsets and their capacity to secrete IL-10 ex vivo in peripheral blood from patients with or without CCD cardiomyopathy. First, we immunophenotyped peripheral blood mononuclear cells from patients according to the expression of markers CD19, CD24, CD38 and CD27 and we showed an expansion of total B cell and transitional CD24highCD38high B cell subsets in CCD patients with cardiac involvement compared to non-infected donors. 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 naïve B10 cells and a tendency to a higher frequency of transitional B10 cells compared to non-infected donors. Our research demonstrates that transitional B cells are greatly expanded in patients with the cardiac form of CCD and these cells retain the ability to secrete IL-10. These findings provide insight into the phenotypic distribution of regulatory B cells in CCD, an important step towards new strategies to prevent cardiomyopathy associated with T. cruzi infection.

Highlights

Chagas disease, a serious health problem caused by the infection with the protozoan parasite Trypanosoma cruzi, comprises an acute and a chronic phase
Four different subsets of peripheral blood B cells can be identified according to the expression levels of surface markers CD24 and CD38: CD19+CD24highCD38high, C D19+CD24intCD38int, CD19+CD24highCD38low and CD19+CD24lowCD38high[26,27]
Results showed that the frequency of transitional B cells (CD24highCD38high) within total B cells was higher in patients with cardiac involvement than in non-infected donors (p = 0.038)

Summary

Introduction

A serious health problem caused by the infection with the protozoan parasite Trypanosoma cruzi, comprises an acute and a chronic phase During the latter, the disease may remain without any detectable symptoms for several decades, or progress toward cardiac or digestive pathological forms, or even a combination of these alterations[1]. There is a bias towards a predominant proinflammatory environment in cardiac patients, while an anti-inflammatory response would prevail in patients without clinical symptoms, data are not completely conclusive[2,3,4] In this context, the regulatory mechanisms that tend to return the immune response to a favorable equilibrium could play a relevant role in the context of Chagas disease. Given that Breg cells have the ability to ameliorate exacerbated inflammatory responses, hampering the development of tissue damage while contributing to pathogen persistence, we sought to analyze ex vivo whether changes in the frequency or phenotypic distribution of B and B10 cells from peripheral blood are associated with clinical outcome of patients with CCD

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