B. abortus RNA INDUCES MHC-I RETENTION IN THE GOLGI APPARATUS VIA TLR8 AND BY DISRUPTING THE ACIDIFICATION OF THIS COMPARTMENT

ALDANA TROTTA; MONICA VERMEULEN; PAULA BARRIONUEVO; MARÍA AYELÉN MILILLO; MARIA VICTORIA DELPINO; GUILLERMO GIAMBARTOLOMEI; FÀBIO VITARELLI MARINHO; SERGIO COSTA OLIVEIRA

Buenos Aires

Congreso; Reunión Conjunta de Biociencias 2017.; 2017

Despite the cytotoxic CD8+ T cell responses elicited by Brucellaabortus, this pathogen is able to survive inside macrophages andgenerate a chronic infection. B. abortus infection of human monocytesdown-modulates the IFN-γ-induced MHC-I cell surface expressionby retaining these molecules in the Golgi apparatus (GA).We have recently demonstrated that B. abortus RNA is the bacterialcomponent involved in this phenomenon. Thus, the aim of this studywas to further characterize the receptor and mechanisms implicatedin MHC-I down-modulation. Endo/phagolysosomal Toll-like receptors(TLR) 3, 7 and 8 are the most known receptors capable ofrecognizing RNA. We had previously discarded TLR3 consequently,to study whether TLR7 and/or TLR8 were involved in the B. abortusRNA-mediated MHC-I down-modulation, THP-1 cells or murinebone marrow macrophages (BMM) were treated with human TLR-7 or TLR-8 agonists in the presence of IFN-γ for 48 h. Then, theexpression of MHC-I molecules was evaluated by flow cytometry.Surpringsily, TLR8 (p