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

M. AYELEN MILILLO; LIS N. VELASQUEZ; M. VICTORIA DELPINO; ALDANA TROTTA; ROBERTO G. POZNER; MARTIN A. ISTURIZ; GUILLERMO H. GIAMBARTOLOMEI; PAULA BARRIONUEVO

Congreso; 58. LXIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI). 18-21 Noviembre de 2015.; 2015

B. Abortus RNA through EGF-like ligands induces the retention of MHC-Imolecules within the Golgi apparatus in human monocytes M. Ayelen Milillo1, Lis N.Velasquez1, M. Victoria Delpino2, Aldana Trotta1, Roberto G. Pozner1, Martin A. Isturiz1, Guillermo H. Giambartolomei2, PaulaBarrionuevo1 1 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 Abstract: Despite the cytotoxic CD8+ T cell responses elicited byBrucella abortus, this intracellular pathogen is capable of surviving insidemacrophages 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, wedemonstrated that B. abortus RNA mimics the intracellular retention of MHC-Iwithin the Golgi apparatus observed with the infection. The aim of this studywas to further characterize the component and pathways involved in MHC-Idown-modulation. For this, RNases-treated B. abortus RNA was employed tostimulate human monocytic THP-1 cells in the presence of IFN-γ for 48 h. Then, the expression of MHC-I molecules wasevaluated by flow cytometry. Surprisingly, completely degraded RNA was able toinhibit MHC-I expression to the same extent as intact RNA (p<0.05),indicating that RNA degradation products are other components implicated inthis phenomenon. We also demonstrated that supernatants from B. abortusRNA-treated cells were able to inhibit MHC-I expression suggesting that thereshould be some soluble mediator involved. Therefore we explored if theEpidermal Growth Factor Receptor (EGFR) pathway could be involved in theRNA-mediated inhibition of MHC-I expression. Neutralization of the EGFR by amonoclonal antibody (Cetuximab) and the inhibition of TNF-α-converting enzyme (TACE) resulted in partial recovery(p<0.05) of MHC-I expression. Overall, these results indicate that MHC-Iintracellular sequestration mediated by B. abortus RNA through EGF-like ligandsis a mechanism whereby these bacteria could avoid cytotoxic CD8+ T cellsrecognition, evading their immunological surveillance.