INVESTIGADORES
GIAMBARTOLOMEI Guillermo Hernan
congresos y reuniones científicas
Título:
Different strategies to inhibit Major Histocompatibility Complex molecules expression employed by Brucella abortus.
Autor/es:
VELÁSQUEZ L. N., M. MILILLO M. A., DELPINO M. V., POZNER R. G., TROTTA A., FERNANDEZ P. M., LANG R., MERCOGLIANO M. F., SCHILLACI R., GIAMBARTOLOMEI G. H., BARRIONUEVO P.
Reunión:
Congreso; LXIII Reunión Anual de la Sociedad Argentina de Inmunología; 2015
Resumen:
Brucella abortusis an intracellular pathogen capable of establishing a chronic infectiondespite eliciting vigorous CD4+ and CD8+ T cellresponses. Previous results demonstrated that B. abortus infectiondiminished the IFN-γ-inducedMHC-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 tofurther study the bacterial components, signalling pathways and mechanismswhereby this bacterium is able to down-modulate the expression of these twomolecules. Our results demonstrate that B. abortus and different mutantstrains are capable of inhibiting MHC-I expression by retaining these moleculeswithin the Golgi apparatus. B. abortus RNA is the bacterial componentinvolved in this phenomenon and neutralization of the EGF receptor (EGFR)resulted in partial recovery of MHC-I expression which indicates that EGF-likeligands could be the soluble mediators employed by B. abortus.Concerning MHC-II, we demonstrated that B. abortus directly diminishesits protein expression. Furthermore, we observed that B. abortusinhibits the IFN-γ-inducedtranscription of MHC-II transactivator (CIITA) and MHC-II genes. Also, wedemonstrated that B. abortus induces the transcription of the negativeregulators of IFN-γ signalling,suppressors of cytokine signalling (SOCS)-1 and 3. These proteins in turn couldbe responsible for the inhibition of CIITA transcription. Overall, theseresults indicate that B. abortus orchestrates remarkably differentstrategies to evade the robust adaptive CD4+ and CD8+ Tcell responses it elicits, preventing the recognition by these cells and promotinga chronic infection.
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