{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:49:14Z","timestamp":1793105354101,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T00:00:00Z","timestamp":1480377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006449","name":"Fundaci\u00f3n Alberto J. Roemmers","doi-asserted-by":"publisher","award":["2012\u20132014"],"award-info":[{"award-number":["2012\u20132014"]}],"id":[{"id":"10.13039\/501100006449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:p><jats:italic>Brucella abortus<\/jats:italic> is able to persist inside the host despite the development of potent CD8<jats:sup>+<\/jats:sup> T\u2010cell responses. We have recently reported the ability of <jats:italic>B. abortus<\/jats:italic> to inhibit the interferon\u2010\u03b3\u2010induced major histocompatibility complex (MHC)\u2010I cell surface expression on human monocytes. This phenomenon was due to the <jats:italic>B. abortus<\/jats:italic>\u2010mediated retention of MHC\u2010I molecules within the Golgi apparatus and was dependent on bacterial viability. However, the implications of bacterial virulence or replicative capacity and the signaling pathways remained unknown. Here we demonstrated that the <jats:italic>B. abortus<\/jats:italic> mutant strains RB51 and <jats:italic>virB10<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic><\/jats:sup> are able to inhibit MHC\u2010I expression in the same manner as wild\u2010type <jats:italic>B. abortus<\/jats:italic>, even though they are unable to persist inside human monocytes for a long period of time. Consistent with this, the phenomenon was triggered early in time and could be observed at 8\u2009h postinfection. At 24 and 48\u2009h, it was even stronger. Regarding the signaling pathway, targeting epidermal growth factor (EGF) receptor (EGFR), ErbB2 (HER2) or inhibition of tumor necrosis factor\u2010\u03b1\u2010converting enzyme, one of the enzymes which generates soluble EGF\u2010like ligands, resulted in partial recovery of MHC\u2010I surface expression. Moreover, recombinant EGF and transforming growth factor\u2010\u03b1 as well as the combination of both were also able to reproduce the <jats:italic>B. abortus<\/jats:italic>\u2010induced MHC\u2010I downmodulation. Finally, when infection was performed in the presence of an extracellular signal\u2013regulated kinase 1\/2 (Erk1\/2) inhibitor, MHC\u2010I surface expression was significantly recovered. Overall, these results describe how <jats:italic>B. abortus<\/jats:italic> evades CD8<jats:sup>+<\/jats:sup> T\u2010cell responses early during infection and exploits the EGFR\u2010ERK signaling pathway to escape from the immune system and favor chronicity.<\/jats:p>","DOI":"10.1038\/icb.2016.111","type":"journal-article","created":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T10:00:58Z","timestamp":1478253658000},"page":"388-398","source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of MHC\u2010I by <i>Brucella abortus<\/i> is an early event during infection and involves EGFR pathway"],"prefix":"10.1111","volume":"95","author":[{"given":"Lis N","family":"Vel\u00e1squez","sequence":"first","affiliation":[{"name":"Instituto de Medicina Experimental (CONICET\u2010Academia Nacional de Medicina)  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M 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