INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Different strategies to inhibit Major Histocompatibility Complex molecules expression employed by Brucella abortus.
Autor/es:
LIS N. VELASQUEZ; M. AYELEN MILILLO; M. VICTORIA DELPINO; ROBERTO G. POZNER; ALDANA TROTTA; PABLO M. FERNANDEZ; ROLAND LANG; M. FLORENCIA MERCOGLIANO; ROXANA SCHILLACI; GUILLERMO H. GIAMBARTOLOMEI; PAULA BARRIONUEVO,
Reunión:
Congreso; 59. LXIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI). 18-21 Noviembre de 2015.; 2015
Resumen:
Different strategies to inhibit Major Histocompatibility Complexmolecules expression employed by Brucella abortusLis N. Velasquez1, M. AyelenMilillo1, M. Victoria Delpino2, Roberto G. Pozner1, Aldana Trotta1, Pablo M. Fernandez2, Roland Lang3, M. Florencia Mercogliano4, RoxanaSchillaci4, Guillermo H. Giambartolomei2, Paula Barrionuevo11 Instituto de Medicina Experimental (CONICET-Academia Nacional deMedicina). Buenos Aires. Argentina 2 Instituto de Inmunología, Genética y Metabolismo (CONICET-UBA).Laboratorio de Inmunogenética. Buenos Aires. Argentina 3 Institut für Klinische Mikrobiologie, Immunologie und Hygiene, UniversitätsklinikumErlangen, Freidrich Alexander Universität Erlangen-Nürnberg. Alemania 4 Instituto de Biología y Medicina Experimental (CONICET). Buenos Aires.Argentina Abstract: Brucella abortus is an intracellular pathogen capable ofestablishing a chronic infection despite eliciting vigorous CD4+ and CD8+ Tcell responses. Previous results demonstrated that B. abortus infectiondiminished the IFN-γ-induced MHC-I andMHC-II surface expression on human monocytes. As a consequence, infectedmacrophages have a decreased capacity to present antigens to CD8+ and CD4+ Tlymphocytes, respectively. The aim of this work was to further study thebacterial components, signalling pathways and mechanisms whereby this bacteriumis able to down-modulate the expression of these two molecules. Our resultsdemonstrate that B. abortus and different mutant strains are capable ofinhibiting MHC-I expression by retaining these molecules within the Golgiapparatus. B. abortus RNA is the bacterial component involved in this phenomenonand neutralization of the EGF receptor (EGFR) resulted in partial recovery ofMHC-I expression which indicates that EGF-like ligands could be the solublemediators employed by B. abortus. Concerning MHC-II, we demonstrated that B.abortus directly diminishes its protein expression. Furthermore, we observedthat B. abortus inhibits the IFN-γ-inducedtranscription of MHC-II transactivator (CIITA) and MHC-II genes. Also, wedemonstrated that B. abortus induces the transcription of the negative regulatorsof IFN-γ signalling, suppressors ofcytokine signalling (SOCS)-1 and 3. These proteins in turn could be responsiblefor the inhibition of CIITA transcription. Overall, these results indicate thatB. abortus orchestrates remarkably different strategies to evade the robustadaptive CD4+ and CD8+ T cell responses it elicits, preventing the recognitionby these cells and promoting a chronic infection.