{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:46:26Z","timestamp":1791942386839,"version":"4.3.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2013,2,19]],"date-time":"2013-02-19T00:00:00Z","timestamp":1361232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Host cytokine responses to\n            <jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>\n            infection are elicited predominantly by the deployment of a type IV secretion system (T4SS). However, the mechanism by which the T4SS elicits inflammation remains unknown. Here we show that translocation of the T4SS substrate VceC into host cells induces proinflammatory responses. Ectopically expressed VceC interacted with the endoplasmic reticulum (ER) chaperone BiP\/Grp78 and localized to the ER of HeLa cells. ER localization of VceC required a transmembrane domain in its N terminus. Notably, the expression of VceC resulted in reorganization of ER structures. In macrophages, VceC was required for\n            <jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>\n            -induced inflammation by induction of the unfolded protein response by a process requiring inositol-requiring transmembrane kinase\/endonuclease 1. Altogether, these findings suggest that translocation of the T4SS effector VceC induces ER stress, which results in the induction of proinflammatory host cell responses during\n            <jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>\n            infection.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:italic>Brucella<\/jats:italic>\n            species are pathogens that require a type IV secretion system (T4SS) to survive in host cells and to maintain chronic infection. By as-yet-unknown pathways, the T4SS also elicits inflammatory responses in infected cells. Here we show that inflammation caused by the T4SS results in part from the sensing of a T4SS substrate, VceC, that localizes to the endoplasmic reticulum (ER), an intracellular site of\n            <jats:italic>Brucella<\/jats:italic>\n            replication. Possibly via binding of the ER chaperone BiP, VceC causes ER stress with concomitant expression of proinflammatory cytokines. Thus, induction of the unfolded protein response may represent a novel pathway by which host cells can detect pathogens deploying a T4SS.\n          <\/jats:p>","DOI":"10.1128\/mbio.00418-12","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T02:56:16Z","timestamp":1361328976000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":130,"title":["Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response"],"prefix":"10.1128","volume":"4","author":[{"given":"Maarten F.","family":"de Jong","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California, Davis, California, USA"},{"name":"Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tregei","family":"Starr","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria G.","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas B.","family":"den Hartigh","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Child","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh A.","family":"Knodler","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Maarten","family":"van Dijl","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Celli","sequence":"additional","affiliation":[{"name":"Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e M.","family":"Tsolis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3167"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01041.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.007"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.008"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","unstructured":"FontanaMF\nBangaS\nBarryKC\nShenX\nTanY\nLuoZQ\nVanceRE\n. 2011. 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