Evento
B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes
Milillo, María Ayelén
; Velasquez, Lis Noelia
; Trotta, Aldana
; Delpino, María Victoria
; Balboa, Luciana
; Giambartolomei, Guillermo Hernan
; Barrionuevo, Paula
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Tipo del evento:
Reunión
Nombre del evento:
LXI Reunión Anual de la Sociedad Agentina de Investigación Clínica; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; VII Reunión Anual de la Sociedad Argentina de Nanomedicina y V Congreso Nacional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Fecha del evento:
15/11/2016
Institución Organizadora:
Sociedad Argentina de Investigación Clínica;
Sociedad Argentina de Inmunología;
Sociedad Argentina de Farmacología Experimental;
Sociedad Argentina de Nanomedicina;
Asociación Argentina De Ciencia y Tecnología De Animales De Laboratorio;
Título del Libro:
Medicina
Título de la revista:
Medicina (Buenos Aires)
Editorial:
Fundación Revista Medicina
ISSN:
1669-9106
Idioma:
Inglés
Clasificación temática:
Resumen
Brucella abortus elicits a strong Th1 immune response whichactivates cytotoxic T lymphocytes. However, this pathogen is ableto survive inside macrophages and generate a chronic infection.Previously we reported that infection of human monocytes/macrophageswith B. abortus inhibits the IFN-γ-induced MHC-I cellsurface expression. More importantly, we have recently demonstratedthat B. abortus RNA, described as a viability-associated(vita)-PAMP, is the bacterial component involved in this phenomenon.Thus, the aim of this study was to further characterize thecomponent, signalling pathways and mechanisms implicated inMHC-I down-modulation. For this, RNases-treated B. abortus RNAwas employed to stimulate human monocytic THP-1 cells in thepresence of IFN-γ for 48 h. Then, the expression of MHC-I moleculeswas evaluated by flow cytometry. Surprisingly, completelydegraded RNA was still able to inhibit MHC-I expression (p<0.05)and it also induced the intracellular retention of these moleculeswithin the Golgi apparatus into the same extent as intact RNA. Onthe contrary, DNase- and Proteinase K-treated RNA as well aseukaryotic RNA controls elicited no effect. Furthermore, B. abortusRNA also inhibited MCH-I expression on human primary monocytesand murine bone-marrow derived macrophages (p<0.05).TLR3 is one of the best known RNA immune receptors, thereforewe evaluated whether it could be involved in this phenomenon.Yet, in the presence of a TLR3 inhibitor, B. abortus RNA downregulated MHC-I expression. On the other hand, neutralization ofthe EGFR resulted in partial recovery (p<0.05) of RNA-mediatedMHC-I inhibition. Overall, these results indicate that the vita-PAMP RNA as well as its degradation products constitute a novelvirulence factor whereby B. abortus, by a TLR3 independentmechanism and through the EGFR pathway, inhibit MHC-I expression.Thus, bacteria can hide within infected cells and avoid theimmunological surveillance of cytotoxic CD8+ T cells.
Palabras clave:
RNA
,
BRUCELLA
,
MHC-I
,
MACROPHAGE
Archivos asociados
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Identificadores
Colecciones
Eventos(IMEX)
Eventos de INST.DE MEDICINA EXPERIMENTAL
Eventos de INST.DE MEDICINA EXPERIMENTAL
Eventos(INIGEM)
Eventos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Eventos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
B. Abortus RNA: a novel vita-pamp involved in the down-modulation of mhc-i expression on human monocytes; LXI Reunión Anual de la Sociedad Agentina de Investigación Clínica; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; VII Reunión Anual de la Sociedad Argentina de Nanomedicina y V Congreso Nacional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2016; 1-2
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