Year-end Sale % OFF 
Abstract
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 T. cruzi 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 ex vivo Breg cell phenotypic distribution although maintain IL-10 production capacity. Here, we sought to identify potential alterations on Breg cells upon in vitro stimulation. Isolated B cells from CCD patients with or without cardiomyopathy and non-infected (NI) donors were stimulated with T. cruzi 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 T. cruzi stimulation diminished the expression of CD24 and CD38 on CD27− B cells while reducing the percentage of CD24high inside CD27+ B cells. Furthermore, T. cruzi 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− B10 cell subsets, while no predominant phenotype was found in the other groups. Patients with cardiomyopathy also displayed higher IL-17 secretion levels in T. cruzi–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 in vitro. Additionally, CCD patients showed an increased frequency of CD24−CD27− B cells and a reduction in the percentage of CD24highCD27+ Breg cells, which appeared to be inversely correlated with the presence of T. cruzi DNA in blood. Finally, CCD patients exhibited a higher frequency of PD-L1+ B cells in T. cruzi–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 T. cruzi and its contribution to chronic Chagas cardiomyopathy.
Highlights
Chagas disease, which etiological agent is the parasite Trypanosoma cruzi, remains affecting about 6 to 7 million people worldwide, mostly in Latin America, and in the United States of America, Canada, and many European and some African, Eastern Mediterranean, and Western Pacific countries (WHO, 2021)
Aiming to characterize Breg cell compartment in patients with chronic Chagas disease (CCD) with different clinical forms and NI donors following T. cruzi stimulation, B cells isolated from PBMC were incubated with T. cruzi lysate or medium only during 48 h with the addition of PIB in the last 5 h of culture, and applied flow cytometry to evaluate the expression of CD24, CD27, and
We further evaluated the percentage of B cell subsets according to CD24-CD27 (Figure 2A) and CD27-CD38 (Figure 2B) markers expression upon T. cruzi stimulation
Summary
Chagas disease, which etiological agent is the parasite Trypanosoma cruzi, remains affecting about 6 to 7 million people worldwide, mostly in Latin America, and in the United States of America, Canada, and many European and some African, Eastern Mediterranean, and Western Pacific countries (WHO, 2021). After infection with the parasite, the innate and adaptive immunity elicited by the host leads to rapid control of the acute parasitemia (Cardoso et al, 2016). The clinical features of the chronic Chagas disease (CCD) vary widely. The immune response, encompassing all its stimulatory and regulatory mediators, is one of the main factors that tilt the balance between the two clinical forms of CCD (Acevedo et al, 2018; Chevillard et al, 2018)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
