S.A. and J.M. contributed equally as first authors.
Mycobacteria-induced granuloma necrosis depends on IRF-1
Version of Record online: 14 AUG 2008
© 2008 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
Journal of Cellular and Molecular Medicine
Volume 13, Issue 8b, pages 2069–2082, August 2009
How to Cite
Aly, S., Mages, J., Reiling, N., Kalinke, U., Decker, T., Lang, R. and Ehlers, S. (2009), Mycobacteria-induced granuloma necrosis depends on IRF-1. Journal of Cellular and Molecular Medicine, 13: 2069–2082. doi: 10.1111/j.1582-4934.2008.00470.x
- Issue online: 26 NOV 2009
- Version of Record online: 14 AUG 2008
- Received: March 19, 2008; Accepted: August 7, 2008
In a mouse model of mycobacteria-induced immunopathology, wild-type C57BL/6 (WT), IL-18-knockout (KO) and IFN-αβ receptor-KO mice developed circumscript, centrally necrotizing granulomatous lesions in response to aerosol infection with M. avium, whereas mice deficient in the IFN-γ receptor, STAT-1 or IRF-1 did not exhibit granuloma necrosis. Comparative, microarray-based gene expression analysis in the lungs of infected WT and IRF-1-KO mice identified a set of genes whose differential regulation was closely associated with granuloma necrosis, among them cathepsin K, cystatin F and matrix metalloprotease 10. Further microarray-based comparison of gene expression in the lungs of infected WT, IFN-γ-KO and IRF-1-KO mice revealed four distinct clusters of genes with variable dependence on the presence of IFN-γ, IRF-1 or both. In particular, IRF-1 appeared to be directly involved in the differentiation of a type I immune response to mycobacterial infection. In summary, IRF-1, rather than being a mere transcription factor downstream of IFN-γ, may be a master regulator of mycobacteria-induced immunopathology.