Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/25270
Title: Down Modulation of Host Immune Response by Amino Acid Repeats Present in a Trypanosoma cruzi Ribosomal Antigen
Authors: Toro-Acevedo, Carlos Alberto
Valente, Bruna M.
Caldas, Gabriela de Assis Burle
Galvão Filho, Bruno
Santiago, Helton da Costa
Arantes, Rosa Maria Esteves
Giusta, Caroline Junqueira
Gazzinelli, Ricardo Tostes
Roffê, Ester
Teixeira, Santuza Maria Ribeiro
Affilliation: Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Patologia Geral. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Instituto de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Abstract: Several antigens from Trypanosoma cruzi, the causative agent of Chagas disease (CD), contain amino acid repeats identified as targets of the host immune response. Ribosomal proteins containing an Ala, Lys, Pro-rich repeat domain are among the T. cruzi antigens that are strongly recognized by antibodies from CD patients. Here we investigated the role of amino acid repeats present in the T. cruzi ribosomal protein L7a, by immunizing mice with recombinant versions of the full-length protein (TcRpL7a), as well as with truncated versions containing only the repetitive (TcRpL7aRep) or the non-repetitive domains (TcRpL7aΔRep). Mice immunized with full-length TcRpL7a produced high levels of IgG antibodies against the complete protein as well as against the repeat domain, whereas mice immunized with TcRpL7aΔRep or TcRpL7aRep produced very low levels or did not produce IgG antibodies against this antigen. Also in contrast to mice immunized with the full-length TcRpL7a, which produced high levels of IFN-γ, only low levels of IFN-γ or no IFN-γ were detected in cultures of splenocytes derived from mice immunized with truncated versions of the protein. After challenging with trypomastigotes, mice immunized with the TcRpL7a were partially protected against the infection whereas immunization with TcRpL7aΔRep did not alter parasitemia levels compared to controls. Strikingly, mice immunized with TcRpL7aRep displayed an exacerbated parasitemia compared to the other groups and 100% mortality after infection. Analyses of antibody production in mice that were immunized with TcRpL7aRep prior to infection showed a reduced humoral response to parasite antigens as well as against an heterologous antigen. In vitro proliferation assays with mice splenocytes incubated with different mitogens in the presence of TcRpL7aRep resulted in a drastic inhibition of B-cell proliferation and antibody production. Taken together, these results indicate that the repeat domain of TcRpL7a acts as an immunosuppressive factor that down regulates the host B-cell response against parasite antigens favoring parasite multiplication in the mammalian host.
Keywords: B-cell
Trypanosoma cruzi
antigen
immune response
immunomodulation
repeat domains
virulence factors
keywords: B-cell
Trypanosoma cruzi
antigenos
resposta imune
Issue Date: 2017
Publisher: Frontiers Research Foundation
Citation: TORO-ACEVEDO, Carlos Alberto et al. Down Modulation of Host Immune Response by Amino Acid Repeats Present in a Trypanosoma cruzi Ribosomal Antigen. Front Microbiol., v. 8, art. 2188, 2017.
DOI: 10.3389/fmicb.2017.02188
ISSN: 1664-302X
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos



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