| First Author | Marquis JF | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 5 | Pages | 3008-15 |
| PubMed ID | 19234196 | Mgi Jnum | J:146243 |
| Mgi Id | MGI:3837081 | Doi | 10.4049/jimmunol.0800680 |
| Citation | Marquis JF, et al. (2009) Disseminated and rapidly fatal tuberculosis in mice bearing a defective allele at IFN regulatory factor 8. J Immunol 182(5):3008-15 |
| abstractText | The interferon regulatory factor (IRF) family member IRF-8 participates in IFN-gamma-dependent transcriptional activation of genes containing in their promoter regions IFN-stimulated response element or IFN-gamma activation site elements. To test the role of IRF-8 in host defenses against tuberculosis, BXH-2 mice, which bear a defective IRF-8(R294C) 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-gamma 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. |
