Trypanosoma cruzi infection down-modulates the immunoproteasome biosynthesis and the MHC class I cell surface expression in HeLa cells

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 pr...

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Veröffentlicht in:PloS one 2014-04, Vol.9 (4), p.e95977-e95977
Hauptverfasser: Camargo, Ricardo, Faria, Liliam O, Kloss, Alexander, Favali, Cecília B F, Kuckelkorn, Ulrike, Kloetzel, Peter-Michael, de Sá, Cezar Martins, Lima, Beatriz D
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container_title PloS one
container_volume 9
creator Camargo, Ricardo
Faria, Liliam O
Kloss, Alexander
Favali, Cecília B F
Kuckelkorn, Ulrike
Kloetzel, Peter-Michael
de Sá, Cezar Martins
Lima, Beatriz D
description 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.
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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24752321</pmid><doi>10.1371/journal.pone.0095977</doi><oa>free_for_read</oa></addata></record>
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subjects Adenoviruses
Antigen presentation
Antigen processing
Antigens
Biology and Life Sciences
Biosynthesis
Catalysis
Cell surface
Chagas Disease - metabolism
Chagas Disease - physiopathology
Chagas' disease
Drug therapy
Gel electrophoresis
Genes, MHC Class I - genetics
Health aspects
HeLa Cells
Humans
Immunoprecipitation
Immunosurveillance
Infections
Interferon
Interferon-gamma - pharmacology
Lymphocytes
Major histocompatibility complex
Medicine and Health Sciences
Parasites
Peptides
Physiological aspects
Polymerase chain reaction
Post-transcription
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Proteins
Proteolysis
Protozoa
Reverse Transcriptase Polymerase Chain Reaction
Trypanosoma cruzi
Trypanosoma cruzi - pathogenicity
Tumor necrosis factor-TNF
Two dimensional analysis
γ-Interferon
title Trypanosoma cruzi infection down-modulates the immunoproteasome biosynthesis and the MHC class I cell surface expression in HeLa cells
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