INVESTIGADORES
GIAMBARTOLOMEI Guillermo Hernan
congresos y reuniones científicas
Título:
B. abortus down-regulates major histocompatibility complex (MHC) class II mature and immature molecules by inhibition of class II transactivator gene expression
Autor/es:
VELÁSQUEZ L. N., DELPINO M. V., FERNÁNDEZ P. M., GIAMBARTOLOMEI, G. H., BARRIONUEVO P
Reunión:
Congreso; LXI Reunión Científica de la Sociedad Argentina de Inmunología; 2013
Resumen:
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. abortusinhibits the expression of MHC-II molecules at very
early points in its production and in this way prevents recognition by T cells