B. abortus RNA through EGF-like ligands induces the retention of MHC-I molecules within the Golgi apparatus in human monocytes.

MILILLO, M. AYELÉN; VELÁSQUEZ, LIS N.; DELPINO, M. VICTORIA; TROTTA, ALDANA; POZNER, ROBERTO G.; ISTURIZ, MARTÍN A.; GIAMBARTOLOMEI, GUILLERMO H.; BARRIONUEVO, PAULA

Buenos Aires

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Inmunología. II Meeting Franco Argentino de Inmunología. IV Reunión de la Sociedad Latinoamericana de Inmunodeficiencias.; 2015

Sociedad Argentina de Inmunología (SAI)

Despite the cytotoxic CD8+ T cell responses elicited by Brucella abortus, this intracellular pathogen is capable of surviving inside macrophages establishing a chronic infection. We recently reported that B. abortus RNA, described as a vita-PAMP, is able to down-modulate the IFN-γ-induced MHC-I expression on human monocytes. Also, we demonstrated that B. abortus RNA mimics the intracellular retention of MHC-I within the Golgi apparatus observed with the infection. The aim of this study was to further characterize the component and pathways involved in MHC-I down-modulation. For this, RNases-treated B. abortus RNA was employed to stimulate human monocytic THP-1 cells in the presence of IFN-γ for 48 h. Then, the expression of MHC-I molecules was evaluated by flow cytometry. Surprisingly, completely degraded RNA was able to inhibit MHC-I expression to the same extent as intact RNA (p 0.05), indicating that RNA degradation products are other components implicated in this phenomenon. We also demonstrated that supernatants from B. abortus RNA-treated cells were able to inhibit MHC-I expression suggesting that there should be some soluble mediator involved. Therefore we explored if the Epidermal Growth Factor Receptor (EGFR) pathway could be involved in the RNA-mediated inhibition of MHC-I expression. Neutralization of the EGFR by a monoclonal antibody (Cetuximab) and the inhibition of TNF-alpha-converting enzyme (TACE) resulted in partial recovery (p 0.05) of MHC-I expression. Overall, these results indicate that MHC-I intracellular sequestration mediated by B. abortus RNA through EGF-like ligands is a mechanism whereby these bacteria could avoid cytotoxic CD8+ T cells recognition, evading their immunological surveillance.