AUTHOR=Girard Magalí C. , Ossowski Micaela S. , Muñoz-Calderón Arturo , Fernández Marisa , Hernández-Vásquez Yolanda , Chadi Raúl , Gómez Karina A. 

TITLE=Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.723549

DOI=10.3389/fcimb.2021.723549

ISSN=2235-2988

ABSTRACT=<p>The clinical evolution of patients with chronic Chagas disease (CCD) is mainly associated with an excessive inflammation and a defective immunomodulatory profile caused by the interaction between <italic>T. cruzi</italic> and the host. Regulatory B (Breg) cells exert immune suppression mostly through IL-10 production (B10 cells), but also through IL-10-independent mechanisms. Previously, we demonstrated that CCD patients with cardiomyopathy show changes in the <italic>ex vivo</italic> Breg cell phenotypic distribution although maintain IL-10 production capacity. Here, we sought to identify potential alterations on Breg cells upon <italic>in vitro</italic> stimulation. Isolated B cells from CCD patients with or without cardiomyopathy and non-infected (NI) donors were stimulated with <italic>T. cruzi</italic> lysate or CpG + CD40L, and characterized by flow cytometry based on the expression of CD24, CD27, CD38, and the regulatory molecules IL-10 and PD-L1. IL-10 and IL-17 secretion in the supernatant of B cells was evaluated by ELISA. Data showed that <italic>T. cruzi</italic> stimulation diminished the expression of CD24 and CD38 on CD27<sup>−</sup> B cells while reducing the percentage of CD24<sup>high</sup> inside CD27<sup>+</sup> B cells. Furthermore, <italic>T. cruzi</italic> induced a regulatory B cell phenotype by increasing B10 cells and IL-10 secretion in all the groups. The innate-like B10 cells expansion observed in patients with cardiomyopathy would be associated with CD27<sup>−</sup> B10 cell subsets, while no predominant phenotype was found in the other groups. Patients with cardiomyopathy also displayed higher IL-17 secretion levels in <italic>T. cruzi</italic>–activated B cells. CpG + CD40L stimulation revealed that B cells from CCD patients and NI donors had the same ability to differentiate into B10 cells and secrete IL-10 <italic>in vitro</italic>. Additionally, CCD patients showed an increased frequency of CD24<sup>−</sup>CD27<sup>−</sup> B cells and a reduction in the percentage of CD24<sup>high</sup>CD27<sup>+</sup> Breg cells, which appeared to be inversely correlated with the presence of <italic>T. cruzi</italic> DNA in blood. Finally, CCD patients exhibited a higher frequency of PD-L1<sup>+</sup> B cells in <italic>T. cruzi</italic>–stimulated samples, suggesting that IL-10-independent mechanisms could also be tangled in the control of inflammation. Altogether, our results provide evidence about the potential role of Breg cells in the immune response developed against <italic>T. cruzi</italic> and its contribution to chronic Chagas cardiomyopathy.</p>