INVESTIGADORES
GIAMBARTOLOMEI Guillermo Hernan
artículos
Título:
Brucella abortus down-regulates MHC class II by the IL-6-dependent inhibition of CIITA through the down-modulation of IFN regulatory factor-1
Autor/es:
VELÁSQUEZ L. N., MILILLO M. A., DELPINO M. V.,TROTTA A., FERNÁNDEZ P., POZNER R. G., LANG R., BALBOA L., GIAMBARTOLOMEI G. H., BARRIONUEVO P.
Revista:
JOURNAL OF LEUKOCYTE BIOLOGY
Editorial:
FEDERATION AMER SOC EXP BIOL
Referencias:
Lugar: Bethesda; Año: 2017 vol. 101 p. 759 - 773
ISSN:
0741-5400
Resumen:
Brucella abortus is an intracellular pathogen capable of surviving inside macrophages.The success of B. abortus as a chronic pathogen relies on its ability toorchestrate different strategies to evade the adaptive CD4+ T cellresponses it elicits. Previously, we demonstrated that B. abortusinhibits the IFN-γ-induced surface expression of MHC-II molecules on humanmonocytes and this phenomenon correlated with a reduction in antigenpresentation. However, the molecular mechanisms whereby B. abortus isable to down-regulate the expression of MHC-II remained to be elucidated. Inthis study we demonstrated that B. abortus infection inhibits theIFN-γ-induced transcription of CIITA and MHC-II genes. Accordingly, we observedthat the synthesis of MHC-II proteins was also diminished. B. abortuswas not only able to reduce the expression of mature MHC-II; it also inhibitedthe expression of invariant-chain-associated immature MHC-II molecules. Outermembrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, diminishedthe expression of MHC-II and CIITA transcripts to the same extent as B.abortus infection. IL-6 contributes to these down-regulatory phenomena. Inaddition, B. abortus and its lipoproteins through IL-6 secretion inducedthe transcription of the negative regulators of IFN-g signaling SOCS-1 and SOCS-3without interfering with STAT1 activation. Yet, B. abortuslipoproteins via IL-6 inhibit the expression of IRF-1, a critical regulatorytranscription factor for CIITA induction. Overall, these results indicate that B.abortus inhibits the expression of MHC-II molecules at very early points intheir synthesis and in this way may prevent recognition by T cells; establishinga chronic infection.