IIBIO   27936
INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Unidad Ejecutora - UE
artículos
Título:
Brucella abortus promotes a fibrotic phenotype in hepatic stellate cells with concomitant autophagy pathway activation
Autor/es:
COMERCI, DIEGO JOSÉ; PESCE VIGLIETTI, AYELÉN IVANA; GIAMBARTOLOMEI, GUILLERMO HERNÁN; HERRMANN, CLAUDIA KARINA; DELPINO, MARÍA VICTORIA; DENNIS, VIDA A.; ARRIOLA BENITEZ, PAULA CONSTANZA; COMERCI, DIEGO JOSÉ; PESCE VIGLIETTI, AYELÉN IVANA; GIAMBARTOLOMEI, GUILLERMO HERNÁN; HERRMANN, CLAUDIA KARINA; DELPINO, MARÍA VICTORIA; DENNIS, VIDA A.; ARRIOLA BENITEZ, PAULA CONSTANZA
Revista:
INFECTION AND IMMUNITY
Editorial:
AMER SOC MICROBIOLOGY
Referencias:
Lugar: Washington; Año: 2018
ISSN:
0019-9567
Resumen:
The liver is frequently affected in patients withactive brucellosis. The present study demonstrates that B. abortus infection induces the activation of the autophagicpathway in hepatic stellate cells to create a microenvironment that promote aprofibrogenic phenotype through the induction of transforming growth factor-β1 (TGF-β1), collagen deposition and inhibition of matrixmetalloproteinase-9 (MMP-9) secretion. Autophagy was revealed by up-regulation of the LC3II/ LC3I ratio andbeclin-1 expression as well as inhibition of p62 expression in infected cells. Theabove findings were dependent on the type IV secretion system (VirB) and thesecreted BPE005 protein; which were partially corroborated using thepharmacological inhibitors wortmannin - a PI3-kinase inhibitor - and leupeptinplus E64 (inhibitors of lysosomalproteases). Activation ofthe autophagic pathway in hepatic stellate cells during Brucella infection could have an important contribution in attenuatinginflammatory hepatic injury by inducing fibrosis. However, with time, B. abortus infection induced beclin-1cleavage with concomitant cleavage of caspase-3 indicating the onset of apoptosisof LX-2 cells, as was confirmed by the TUNEL assay and Hoechst staining. These results demonstrate thatthe crosstalk of LX-2 cells and B.abortus induces autophagy and fibrosis with concomitant apoptosis of LX-2cells, which may explain some potential mechanisms of liver damage observed inhuman brucellosis.