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The present study demonstrates that\n            <jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>\n            infection induces the activation of the autophagic pathway in hepatic stellate cells to create a microenvironment that promotes a profibrogenic phenotype through the induction of transforming growth factor-\u03b21 (TGF-\u03b21), collagen deposition, and inhibition of matrix metalloproteinase-9 (MMP-9) secretion. Autophagy was revealed by upregulation of the LC3II\/LC3I ratio and Beclin-1 expression as well as inhibition of p62 expression in infected cells. The above-described findings were dependent on the type IV secretion system (VirB) and the secreted BPE005 protein, which were partially corroborated using the pharmacological inhibitors wortmannin, a phosphatidyl inositol 3-kinase inhibitor, and leupeptin plus E64 (inhibitors of lysosomal proteases). Activation of the autophagic pathway in hepatic stellate cells during\n            <jats:named-content content-type=\"genus-species\">Brucella<\/jats:named-content>\n            infection could have an important contribution to attenuating inflammatory hepatic injury by inducing fibrosis. However, with time,\n            <jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>\n            infection induced Beclin-1 cleavage with concomitant cleavage of caspase-3, indicating the onset of apoptosis of LX-2 cells, as was confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay and Hoechst staining. These results demonstrate that the cross talk of LX-2 cells and\n            <jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>\n            induces autophagy and fibrosis with concomitant apoptosis of LX-2 cells, which may explain some potential mechanisms of liver damage observed in human brucellosis.\n          <\/jats:p>","DOI":"10.1128\/iai.00522-17","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T00:50:17Z","timestamp":1507596617000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Brucella abortus Promotes a Fibrotic Phenotype in Hepatic Stellate Cells, with Concomitant Activation of the Autophagy Pathway"],"prefix":"10.1128","volume":"86","author":[{"given":"Paula Constanza","family":"Arriola Benitez","sequence":"first","affiliation":[{"name":"Instituto de Inmunolog\u00eda, Gen\u00e9tica y Metabolismo (INIGEM), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayel\u00e9n Ivana","family":"Pesce Viglietti","sequence":"additional","affiliation":[{"name":"Instituto de Inmunolog\u00eda, Gen\u00e9tica y Metabolismo (INIGEM), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia Karina","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Dr. Rodolfo A. 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