title: Trypanosoma cruzi infection down-modulates the immunoproteasome biosynthesis and the MHC class I cell surface expression in HeLa cells.
abstract: Generally, Trypanosoma cruzi infection in human is persistent and tends to chronicity, suggesting that the parasite evade the immune surveillance by down regulating the intracellular antigen processing routes. Within the MHC class I pathway, the majority of antigenic peptides are generated by the proteasome. However, upon IFN-γ stimulation, the catalytic constitutive subunits of the proteasome are replaced by the subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 to form the immunoproteasome. In this scenario, we analyzed whether the expression and activity of the constitutive and the immunoproteasome as well as the expression of other components of the MHC class I pathway are altered during the infection of HeLa cells with T. cruzi. By RT-PCR and two-dimensional gel electrophoresis analysis, we showed that the expression and composition of the constitutive proteasome is not affected by the parasite. In contrast, the biosynthesis of the β1i, β2i, β5i immunosubunits, PA28β, TAP1 and the MHC class I molecule as well as the proteasomal proteolytic activities were down-regulated in infected-IFN-γ-treated cell cultures. Taken together, our results provide evidence that the protozoan T. cruzi specifically modulates its infection through an unknown posttranscriptional mechanism that inhibits the expression of the MHC class I pathway components.
authors.affiliation: Departamento de Biologia Celular, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília, Distrito Federal, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Camargo
authors.affiliation: Departamento de Biologia Celular, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília, Distrito Federal, Brazil.
authors.forename: Liliam O
authors.initials: LO
authors.lastname: Faria
authors.affiliation: Institute für Biochimie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kloss
authors.affiliation: Departamento de Biologia Celular, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília, Distrito Federal, Brazil.
authors.forename: Cecília B F
authors.initials: CB
authors.lastname: Favali
authors.affiliation: Institute für Biochimie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kuckelkorn
authors.affiliation: Institute für Biochimie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Kloetzel
authors.affiliation: Departamento de Biologia Celular, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília, Distrito Federal, Brazil.
authors.forename: Cezar Martins
authors.initials: CM
authors.lastname: de Sá
authors.affiliation: Departamento de Biologia Celular, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasília, Distrito Federal, Brazil.
authors.forename: Beatriz D
authors.initials: BD
authors.lastname: Lima
mesh_terms: D014355:Chagas Disease / Q000378:metabolism* / Q000503:physiopathology*; D005805:Genes, MHC Class I / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
chemical_list: D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex
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