{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:11:42Z","timestamp":1791198702350,"version":"4.1.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic inflammation activates the tryptophan-degrading enzyme IDO, which is well known to impair T cell proliferation. We have previously established that bacille Calmette-Gu\u00e9rin (BCG), an attenuated form of Mycobacterium bovis, is associated with persistent activation of IDO in the brain and chronic depressive-like behavior, but a causative role has not been established. In these experiments we used both pharmacologic and genetic approaches to test the hypothesis that IDO activation is responsible for the development of chronic depression that follows BCG infection. BCG induced TNF-\u03b1, IFN-\u03b3, and IDO mRNA steady-state transcripts in the brain as well as the enzyme 3-hydroxyanthranilic acid oxygenase (3-HAO) that lies downstream of IDO and generates the neuroactive metabolite, quinolinic acid. Behaviors characteristic of depression were apparent 1 wk after BCG infection. Pretreatment with the competitive IDO inhibitor 1-methyltryptophan fully blocked BCG-induced depressive-like behaviors. Importantly, IDO-deficient mice were completely resistant to BCG-induced depressive-like behavior but responded normally to BCG induction of proinflammatory cytokines. These results are the first to prove that the BCG-induced persistent activation of IDO is accompanied by the induction of 3-hydroxyanthranilic acid oxygenase and that IDO is required as an initial step for the subsequent development of chronic depressive-like behavior.<\/jats:p>","DOI":"10.4049\/jimmunol.0802722","type":"journal-article","created":{"date-parts":[[2009,2,20]],"date-time":"2009-02-20T17:41:32Z","timestamp":1235151692000},"page":"3202-3212","source":"Crossref","is-referenced-by-count":256,"title":["Induction of IDO by Bacille Calmette-Gu\u00e9rin Is Responsible for Development of Murine Depressive-Like Behavior"],"prefix":"10.1093","volume":"182","author":[{"given":"Jason C","family":"O'Connor","sequence":"first","affiliation":[{"name":"Integrative Immunology and Behavior Program, Department of Animal Sciences, College of Agriculture, Consumer, and Environmental Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus A","family":"Lawson","sequence":"additional","affiliation":[{"name":"Integrative Immunology and Behavior Program, Department of Animal Sciences, College of Agriculture, Consumer, and Environmental Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Integrative Immunology and Behavior Program, Department of Animal Sciences, College of Agriculture, Consumer, and Environmental Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M","family":"Briley","sequence":"additional","affiliation":[{"name":"Section on Functional Neuroanatomy, National Institute of Mental Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra S","family":"Szegedi","sequence":"additional","affiliation":[{"name":"Integrative Immunology and Behavior Program, Department of Animal Sciences, College of Agriculture, Consumer, and Environmental Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Lestage","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Agronomique, Centre National de la Recherche Scientifique, University Victor Segalen Bordeaux II , Bordeaux,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Castanon","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Agronomique, Centre National de la Recherche Scientifique, University Victor Segalen Bordeaux II , Bordeaux,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles","family":"Herkenham","sequence":"additional","affiliation":[{"name":"Section on Functional Neuroanatomy, National Institute of Mental Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Dantzer","sequence":"additional","affiliation":[{"name":"Integrative Immunology and Behavior Program, Department of Animal Sciences, College of Agriculture, Consumer, and Environmental Sciences"},{"name":"Department of Pathology, College of Medicine, University of Illinois at Urbana-Champaign , Urbana, IL 61801"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith W","family":"Kelley","sequence":"additional","affiliation":[{"name":"Integrative Immunology and Behavior Program, Department of Animal Sciences, College of Agriculture, Consumer, and Environmental Sciences"},{"name":"Department of Pathology, College of Medicine, University of Illinois at Urbana-Champaign , Urbana, IL 61801"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,3,1]]},"reference":[{"key":"2026012807031154200_R1","volume-title":"Tuberculosis Facts","year":"2008"},{"key":"2026012807031154200_R2","first-page":"S33","article-title":"Annulling a dangerous liaison: vaccination strategies against AIDS and tuberculosis.","volume-title":"Nat. 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