Signatures of CD4+ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy

Front Immunol. 2024 Apr 25:15:1385850. doi: 10.3389/fimmu.2024.1385850. eCollection 2024.

Abstract

Introduction: Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi. While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).

Methods: Here, we employed high-dimensional flow cytometry to analyze CD4+ T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms.

Results: Effector CD27-CD4+ T cells were expanded in both CCC groups, and only mild CCC patients showed higher frequencies of effector memory and T follicular helper (Tfh) cells than healthy donors (CTL) and asymptomatic patients. Unsupervised analysis confirmed these findings and further revealed the expansion of a specific subpopulation composed of Tfh, transitional, and central memory CD4+ T cells bearing a phenotype associated with strong activation, differentiation, and exhaustion in patients with mild but not moderate/severe CCC. In contrast, patients with mild and moderate/severe CCC had lower frequencies of CD4+ T cells expressing lower levels of activation markers, suggesting resting status, than CTL. Regarding the B cell compartment, no alterations were found in naïve CD21-, memory cells expressing IgM or IgD, marginal zone, and plasma cells in patients with Chagas disease. However, expansion of class-switched activated and atypical memory B cells was observed in all clinical forms, and more substantially in mild CCC patients.

Discussion: Taken together, our results showed that T. cruzi infection triggers changes in CD4+ T and B cell compartments that are more pronounced in the mild CCC clinical form, suggesting an orchestrated cellular communication during Chagas disease.

Conclusion: Overall, these findings reinforce the heterogeneity and complexity of the immune response in patients with chronic Chagas disease and may provide new insights into disease pathology and potential markers to guide clinical decisions.

Keywords: B cells; CD4 + T cells; Trypanosoma cruzi; cardiomyopathy; chagas disease; effector; memory; multifunctional.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes* / immunology
  • Chagas Cardiomyopathy* / immunology
  • Chronic Disease
  • Female
  • Humans
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Trypanosoma cruzi / immunology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), INCT-Vacinas (465293/2014-0, CBB-APQ-03608-17), National Institutes of Health, FIOCRUZ, Programa Institucional de Internacionalização -CAPES -PrInt (CAPES PrInt -Program for Institutional Internationalization), Fundação Oswaldo Cruz (FIOCRUZ), and by the intramural research program of the NIAID, NIH, USA (ER, AS, DJ, IR, TL, MR), the Flow Cytometry Core Facility at VRC and Fiocruz-MG. LRVA, ATC, and OAMF are CNPq fellows (PQ). OAMF receives financial support from Universidade do Estado do Amazonas-UEA (PROVISIT N° 005/2023-PROPESP/UEA). The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.