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

MILILLO MA; TROTTA A; MARINHO FV; DELPINO MV; VELÁSQUEZ LN; VERMEULEN M; OLIVERIA SC; GIAMBARTOLOMEI GH; BARRIONUEVO P

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

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