{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:38:46Z","timestamp":1778837926330,"version":"3.51.4"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"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":["Infect Immun"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Virulent mycobacterial infections progress slowly, with a latent period that leads to clinical disease in a proportion of cases.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium avium<\/jats:named-content>subsp.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">paratuberculosis<\/jats:named-content>is an intracellular pathogen that causes paratuberculosis or Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally reported to have a role in intracellular pathogen killing and has since been shown to have an important immunoregulatory role in chronic immune diseases. Here we demonstrate an association between increased IDO levels and progression to clinical mycobacterial disease in a natural host, characterizing gene expression, protein localization, and functional effects. IDO mRNA levels were significantly increased in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. avium<\/jats:named-content>subsp.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">paratuberculosis<\/jats:named-content>-infected monocytic cells. Levels of both IDO gene and protein expression were significantly upregulated within the affected tissues of sheep with JD, particularly at the site of primary infection, the ileum, of animals with severe multibacillary disease. Lesion severity was correlated with the level of IDO gene expression. IDO gene expression was also increased in the peripheral blood cells of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. avium<\/jats:named-content>subsp.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">paratuberculosis<\/jats:named-content>-exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were functional, as shown by decreased plasma tryptophan levels, which correlated with the onset of clinical signs, a stage well known to be associated with Th1 immunosuppression. IDO may be involved in downregulating immune responses to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. avium<\/jats:named-content>subsp.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">paratuberculosis<\/jats:named-content>and other virulent mycobacteria, which may be an example of the pathogen harnessing host immunoregulatory pathways to aid survival. These findings raise new questions about the host-mycobacterium interactions in the progression from latent to clinical disease.<\/jats:p>","DOI":"10.1128\/iai.05204-11","type":"journal-article","created":{"date-parts":[[2011,7,6]],"date-time":"2011-07-06T03:06:44Z","timestamp":1309921604000},"page":"3821-3832","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections"],"prefix":"10.1128","volume":"79","author":[{"given":"Karren M.","family":"Plain","sequence":"first","affiliation":[{"name":"Farm Animal and Veterinary Public Health, Faculty of Veterinary Science, University of Sydney, Camden, New South Wales 2570, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumudika","family":"de Silva","sequence":"additional","affiliation":[{"name":"Farm Animal and Veterinary Public Health, Faculty of Veterinary Science, University of Sydney, Camden, New South Wales 2570, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Earl","sequence":"additional","affiliation":[{"name":"Biochemistry Department, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas J.","family":"Begg","sequence":"additional","affiliation":[{"name":"Farm Animal and Veterinary Public Health, Faculty of Veterinary Science, University of Sydney, Camden, New South Wales 2570, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Auriol C.","family":"Purdie","sequence":"additional","affiliation":[{"name":"Farm Animal and Veterinary Public Health, Faculty of Veterinary Science, University of Sydney, Camden, New South Wales 2570, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Whittington","sequence":"additional","affiliation":[{"name":"Farm Animal and Veterinary Public Health, Faculty of Veterinary Science, University of Sydney, Camden, New South Wales 2570, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801212"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1615-9861(200205)2:5<551::AID-PROT551>3.0.CO;2-O"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.12.004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2009.09.007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2189"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.12.032"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2010.06.016"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.5.2910"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(01)00351-8"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-0813.2006.00001.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.45.1.29"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-191197"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9975(97)80001-1"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2008.02.017"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/0300985810375049"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2009.01.014"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.10.007"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2002.01378.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/039463200802100205"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01195.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.6.2249"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2008.07.021"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.3.489-512.2001"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6156-6164.2001"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0147-9571(02)00070-X"},{"key":"e_1_3_3_27_2","first-page":"453","article-title":"Interpretation of the gamma interferon test for diagnosis of subclinical paratuberculosis in cattle","volume":"9","author":"Jungersen G.","year":"2002","unstructured":"JungersenG.HudaA.HansenJ. 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