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Brucella abortus down-regulates MHC class II by the IL-6-dependent inhibition of CIITA through the downmodulation of IFN regulatory factor-1 (IRF-1).
Velásquez, Lis N; Milillo, M Ayelén; Delpino, M Victoria; Trotta, Aldana; Fernández, Pablo; Pozner, Roberto G; Lang, Roland; Balboa, Luciana; Giambartolomei, Guillermo H; Barrionuevo, Paula.
Afiliação
  • Velásquez LN; Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires, Argentina.
  • Milillo MA; Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires, Argentina.
  • Delpino MV; Instituto de Inmunología, Genética y Metabolismo, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina; and.
  • Trotta A; Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires, Argentina.
  • Fernández P; Instituto de Inmunología, Genética y Metabolismo, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina; and.
  • Pozner RG; Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires, Argentina.
  • Lang R; Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Freidrich Alexander Universität Erlangen-Nürnberg, Germany.
  • Balboa L; Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires, Argentina.
  • Giambartolomei GH; Instituto de Inmunología, Genética y Metabolismo, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina; and.
  • Barrionuevo P; Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires, Argentina; pbarrion2004@yahoo.com.ar.
J Leukoc Biol ; 101(3): 759-773, 2017 03.
Article em En | MEDLINE | ID: mdl-27765819
ABSTRACT
Brucella abortus is an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortus as a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4+ T cell responses that it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B. abortus is able to down-regulate the expression of MHC-II, remained to be elucidated. In this study, we demonstrated that B. abortus infection inhibits the IFN-γ-induced transcription of MHC-II, transactivator (CIITA) and MHC-II genes. Accordingly, we observed that the synthesis of MHC-II proteins was also diminished. B. abortus was not only able to reduce the expression of mature MHC-II, but it also inhibited the expression of invariant chain (Ii)-associated immature MHC-II molecules. Outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, diminished the expression of MHC-II and CIITA transcripts to the same extent as B. abortus infection. IL-6 contributes to these down-regulatory phenomena. In addition, B. abortus and its lipoproteins, through IL-6 secretion, induced the transcription of the negative regulators of IFN-γ signaling, suppressor of cytokine signaling (SOCS)-1 and -3, without interfering with STAT1 activation. Yet, B. abortus lipoproteins via IL-6 inhibit the expression of IFN regulatory factor 1 (IRF-1), a critical regulatory transcription factor for CIITA induction. Overall, these results indicate that B. abortus inhibits the expression of MHC-II molecules at very early points in their synthesis and in this way, may prevent recognition by T cells establishing a chronic infection.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Brucella abortus / Proteínas Nucleares / Antígenos de Histocompatibilidade Classe II / Regulação para Baixo / Transativadores / Interleucina-6 / Fator Regulador 1 de Interferon Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: J Leukoc Biol Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Argentina

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Brucella abortus / Proteínas Nucleares / Antígenos de Histocompatibilidade Classe II / Regulação para Baixo / Transativadores / Interleucina-6 / Fator Regulador 1 de Interferon Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: J Leukoc Biol Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Argentina