{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:59:04Z","timestamp":1772787544254,"version":"3.50.1"},"reference-count":43,"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>The interferon regulatory factor (IRF) family member IRF-8 participates in IFN-\u03b3-dependent transcriptional activation of genes containing in their promoter regions IFN-stimulated response element or IFN-\u03b3 activation site elements. To test the role of IRF-8 in host defenses against tuberculosis, BXH-2 mice, which bear a defective IRF-8R294C allele, were challenged with low doses of virulent Mycobacterium tuberculosis via the i.v. and aerosol routes. BXH-2 mice were found to be extremely susceptible to M. tuberculosis, as demonstrated by rapid and uncontrolled microbial replication in spleen, liver, and lungs leading to very early death. The BXH-2 defect was expressed very early (10 days postinfection) as uncontrolled intracellular pathogen replication in NOS2-expressing lung macrophages, impaired granuloma formation, rapid dissemination of the infection to distant sites, and rapid necrosis of infected tissues. There was complete absence of IL-12p40 induction, severely reduced IFN-\u03b3 production, and impaired T cell priming in the lungs of infected BXH-2, highlighting the critical role of IRF-8 in this process. Collectively, these results identify IRF-8 as a critical regulator of host defenses against tuberculosis.<\/jats:p>","DOI":"10.4049\/jimmunol.0800680","type":"journal-article","created":{"date-parts":[[2009,2,20]],"date-time":"2009-02-20T17:41:32Z","timestamp":1235151692000},"page":"3008-3015","source":"Crossref","is-referenced-by-count":35,"title":["Disseminated and Rapidly Fatal Tuberculosis in Mice Bearing a Defective Allele at IFN Regulatory Factor 8"],"prefix":"10.1093","volume":"182","author":[{"given":"Jean-Fran\u00e7ois","family":"Marquis","sequence":"first","affiliation":[{"name":"Centre for the Study of Host Resistance, Department of Biochemistry, McGill University , Montreal, Quebec,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"LaCourse","sequence":"additional","affiliation":[{"name":"Trudeau Institute , Saranac Lake, NY 12983"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Ryan","sequence":"additional","affiliation":[{"name":"Trudeau Institute , Saranac Lake, NY 12983"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J","family":"North","sequence":"additional","affiliation":[{"name":"Trudeau Institute , Saranac Lake, NY 12983"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Gros","sequence":"additional","affiliation":[{"name":"Centre for the Study of Host Resistance, Department of Biochemistry, McGill University , Montreal, Quebec,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,3,1]]},"reference":[{"key":"2026012806362435600_R1","article-title":"The World Health Report 2000.","volume-title":"Health Systems: Improving Performance","year":"2000"},{"key":"2026012806362435600_R2","volume-title":"Global Tuberculosis Control: Surveillance, Planning. 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