FERNANDEZ Pablo Mariano
congresos y reuniones científicas
Mechanisms involved in Major Histocompatibility Complex (MHC) class II down-regulation mediated by B. abortus on human monocytes
VELÁSQUEZ, L N; DELPINO, M V; FERNANDEZ, PABLO M.; GAIMBARTOLOMEI, G H; BARRIONUEVO, P
Waterville Valley, NH
Congreso; Phagocytes Gordon Research Conference; 2013
Gordon Research Conference
Brucella abortus is an intracellular pathogen capable of surviving inside macrophages for many years. In order to survive inside the host and establish a chronic infection, 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 Infect Immun. 2008 Jan; 76(1):250-62). 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 and MHC-II genes. Accordingly, we observed by Western Blot and confocal microscopy that the synthesis of MHC-II proteins was also diminished. 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 molecules. 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. Further studies will be needed to determine whether B. abortus is in fact interfering with the signaling of IFN-γ to generate all these responses or it is using a more direct approach that only targets MHC-II molecules. Furthermore, failure in antigen presentation could also be induced by interfering with the processing machinery. In this scenario, the study of different molecules involved in antigen processing will also be relevant. In conclusion, B. abortus could be employing different strategies to conceal itself inside macrophages and evade host immunity.