INVESTIGADORES
FERNANDEZ Pablo Mariano
congresos y reuniones científicas
Título:
DIFFERENT STRATEGIES TO INHIBIT MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULES EXPRESSION EMPLOYED BY BRUCELLA ABORTUS.
Autor/es:
LIS VELÁSQUEZ; MA MILILLO ; MV DELPINO; RG POZNER; A TROTTA; P FERNANDEZ; R LANG; MF MERCOGLIANO; R SCHILLACI; GH GIAMBARTOLOMEI; P BARRIONUEVO
Lugar:
C.A.B.A.
Reunión:
Congreso; LXIII Argentinean Society for Immunolgy Meeting; 2015
Resumen:
Brucella abortus is an intracellular pathogen capable of establishing a chronic infection despite eliciting vigorous CD4+ and CD8+ T cell responses. Previous results demonstrated that B. abortus infection diminished the IFN-γ-induced MHC-I and MHC-II surface expression on human monocytes. As a consequence, infected macrophages have a decreased capacity to present antigens to CD8+ and CD4+ T lymphocytes, respectively. The aim of this work was to further study the bacterial components, signalling pathways and mechanisms whereby this bacterium is able to down-modulate the expression of these two molecules. Our results demonstrate that B. abortus and different mutant strains are capable of inhibiting MHC-I expression by retaining these molecules within the Golgi apparatus. B. abortus RNA is the bacterial component involved in this phenomenon and neutralization of the EGF receptor (EGFR) resulted in partial recovery of MHC-I expression which indicates that EGF-like ligands could be the soluble mediators employed by B. abortus. Concerning MHC-II, we demonstrated that B. abortus directly diminishes its protein expression. Furthermore, we observed that B. abortus inhibits the IFN-γ-induced transcription of MHC-II transactivator (CIITA) and MHC-II genes. Also, we demonstrated that B. abortus induces the transcription of the negative regulators of IFN-γ signalling, suppressors of cytokine signalling (SOCS)-1 and 3. These proteins in turn could be responsible for the inhibition of CIITA transcription. Overall, these results indicate that B. abortus orchestrates remarkably different strategies to evade the robust adaptive CD4+ and CD8+ T cell responses it elicits, preventing the recognition by these cells and promoting a chronic infection.
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