B. ABORTUS DOWN-REGULATES MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS II MATURE AND IMMATURE MOLECULES BY INHIBITION OF CLASS II TRANSACTIVATOR GENE EXPRESSION

VELAZQUEZ LIS; DELPINO M. VICTORIA; FERNANDEZ PABLO; GIAMBARTALOMEI, GUILLERMO; BARRIONUEVO PAULA

Los Cocos, Cordoba

Congreso; LX1 Reunión Anual de la Sociedad Argentina de Inmunología (SAI). 4-7 Noviembre 2013.; 2013

Brucella abortus is an intracellular pathogen capable of surviving inside macrophages and establishing a chronic infection. In order to survive inside the host, this bacterium must trigger different strategies to evade the robust adaptive CD4+ T cell response it elicits. Previously we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC-II molecules on human monocytes. This phenomenon was mediated by B. abortus outer membrane lipoproteins and through the secretion of IL-6. Moreover, this diminished expression of MHC-II molecules correlated with a reduction in antigen presentation. However, the molecular mechanism by which B. abortus is able to down-regulate the expression of MHC-II molecules remained to be elucidated. In this study, we demonstrated that infection with B. abortus inhibits the IFN-γ-induced transcription of the class II transactivator (CIITA) (p<0.01) and MHC-II (p<0.001) genes. Accordingly, we observed by Western Blot and confocal microscopy that the synthesis of MHC-II proteins was also diminished (p<0.05 and p<0.01). B. abortus was not only able to reduce the expression of mature MHC-II molecules; it also inhibited the expression of invariant-chain-associated MHC-II immature molecules (p<0.05). Also, we corroborated that MHC-II down-regulatory mechanisms induced by B. abortus infection were mediated by B. abortus lipoproteins. Interestingly, B. abortus and their lipoproteins induced Suppressor of Cytokine Signaling-1 (SOCS-1) and SOCS-3 gene transcription and these proteins may be responsible for attenuating IFN-γ-induced CIITA and MHC-II expression in human monocytes. Taken together, these results indicate that B. abortus inhibits the expression of MHC-II molecules at very early points in its production and in this way prevents recognition by T cells.