부산대학교 도서관

Molecular mechanisms employed by B. abortusto inhibit MHC-II surface expression, in order to evade host immunity and establish a chronic infection. Brucella abortusis an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortusas a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4+T cell responses that it elicits. Previously, we demonstrated that B. abortusinhibits the IFN-?-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B. abortusis able to down-regulate the expression of MHC-II, remained to be elucidated. In this study, we demonstrated that B. abortusinfection inhibits the IFN-?-induced transcription of MHC-II, transactivator (CIITA) and MHC-II genes. Accordingly, we observed that the synthesis of MHC-II proteins was also diminished. B. abortuswas not only able to reduce the expression of mature MHC-II, but it also inhibited the expression of invariant chain (Ii)-associated immature MHC-II molecules. Outer membrane protein 19 (Omp19), a prototypical B. abortuslipoprotein, diminished the expression of MHC-II and CIITA transcripts to the same extent as B. abortusinfection. IL-6 contributes to these down-regulatory phenomena. In addition, B. abortusand its lipoproteins, through IL-6 secretion, induced the transcription of the negative regulators of IFN-? signaling, suppressor of cytokine signaling (SOCS)-1 and -3, without interfering with STAT1 activation. Yet, B. abortuslipoproteins via IL-6 inhibit the expression of IFN regulatory factor 1 (IRF-1), a critical regulatory transcription factor for CIITA induction. Overall, these results indicate that B. abortusinhibits the expression of MHC-II molecules at very early points in their synthesis and in this way, may prevent recognition by T cells establishing a chronic infection.