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Front. Immunol. | doi: 10.3389/fimmu.2018.03015

Activation of human CD11b+ B1 B-cells by Trypanosoma cruzi-derived proteins is associated with protective immune response in human Chagas disease

 Livia S. Passos1, 2, 3, Luisa M. Magalhães1, 2, 3, Rodrigo P. Soares2, 3, 4,  Alexandre F. Marques2, 3,  Marina L. Alves1, 3,  Rodolfo C. Giunchetti1, 2, 3, Maria do Carmo P. Nunes3,  Kenneth J. Gollob5, 6 and  Walderez O. Dutra1, 2, 3, 5*
  • 1Morphology, Universidade Federal de Minas Gerais, Brazil
  • 2Universidade Federal de Minas Gerais, Brazil
  • 3Clínica Médica, Pós-graduação em Medicina Tropical, Universidade Federal de Minas Gerais, Brazil
  • 4Fiocruz Research Center Renê Rachou, Brazil
  • 5Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais (INCT), Brazil
  • 6AC Camargo Cancer Center, Brazil

B-cells mediate humoral adaptive immune response via the production of antibodies and cytokines, and by inducing T-cell activation. These functions can be attributed to distinct B-cell subpopulations. Infection with Trypanosoma cruzi, the causative agent of Chagas disease, induces a polyclonal B-cell activation and lytic antibody production, critical for controlling parasitemia. Individuals within the chronic phase of Chagas disease may remain in an asymptomatic form (indeterminate), or develop severe cardiomyopathy (cardiac form) that can lead to death. Currently, there is no effective vaccine to prevent Chagas disease, and no treatment to halt the development of the cardiomyopathy once it is installed. The pathology associated with cardiac Chagas disease is a result of an inflammatory reaction. Thus, discovering characteristics of the host’s immune response that favor the maintenance of favorable heart function may unveil important immunotherapeutic targets. Given the importance of B cells in antibody production and parasite control, we investigated T. cruzi-derived antigenic fractions responsible for B-cell activation and whether frequencies and functional characteristics of B-cell subpopulations are associated with different clinical outcomes of human Chagas disease. We stimulated cells from indeterminate (I) and cardiac (C) Chagas patients, and non-infected individuals (NI), with T. cruzi-derived protein- (PRO), glycolipid- (GCL) and lipid (LIP)-enriched fractions and determined functional characteristics of B-cell subpopulations. Our results showed that the frequency of B-cells was similar amongst groups. PRO, but not GCL nor LIP, led to an increased frequency of B1 B-cells in I, but not C nor NI. Although stimulation with PRO induced higher TNF expression by B1 B-cells from C and I, as compared to NI, it induced expression of IL-10 in cells from I, but not C. Stimulation with PRO induced an increased frequency of the CD11b+ B1 B-cell subpopulation, which was associated with better cardiac function. Chagas patients displayed increased IgM production, and activation of gamma-delta T-cells, which have been associated with B1 B-cell function. Our data showed that PRO activates CD11b+ B1 B-cells, and that this activation is associated with a beneficial clinical status. These findings may have implications in designing new strategies focusing on B-cell activation to prevent Chagas disease cardiomyopathy.

Keywords: B1 B-cells, Chagas Disease, cardiomyopathy, Trypanosoma-cruzi, Immunoregulation, Cytokines

Received: 14 Mar 2018; Accepted: 05 Dec 2018.

Edited by:

Emilio L. Malchiodi, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina

Reviewed by:

Paul Fisch, University Hospital Freiburg, Germany
M. Victoria Delpino, CONICET Instituto de Inmunología, Genética y Metabolismo (INIGEM), Argentina  

Copyright: © 2018 Passos, Magalhães, Soares, Marques, Alves, Giunchetti, Nunes, Gollob and Dutra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Walderez O. Dutra, Universidade Federal de Minas Gerais, Morphology, Belo Horizonte, Brazil, waldutra@gmail.com