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(American Journal of Pathology. 2001;158:361-366.)
© 2001 American Society for Investigative Pathology

Short Communication

Disruption of Nuclear Factor-Interleukin-6, a Transcription Factor, Results in Severe Mycobacterial Infection

Isamu Sugawara^*, Satoru Mizuno^*, Hiroyuki Yamada^*, Makoto Matsumoto and Shizuo Akira

From the Department of Molecular Pathology,^*
The Research Institute of Tuberculosis, Kiyose, Tokyo; and the Department of Host Defense,
Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Nuclear factor-interleukin-6 (NF-IL-6) is one of several nuclear transcription factors (NF-IL-6, NF-B, PU.1, interferon-regulatory factor 1, Egr-1, and Stat-1). NF-IL-6 and NF-B are expressed in macrophages and is induced by bacterial lipopolysaccharides. To evaluate whether NF-IL-6 is required for the inflammatory immune response to mycobacterial infection, in which epithelioid macrophages comprise the leading cell population, we generated NF-IL-6 knockout (KO) mutant mice. Airborne infection of these mice with Mycobacterium tuberculosis strains induced disseminated tuberculosis lacking granuloma formation, although interferon-, tumor necrosis factor-, and interleukin-12 mRNA expression levels were within the normal range compared with those of wild-type mice. Generation of O₂^- and mycobacterial killing by neutrophils from these mice were impaired severely compared with wild-type mice. We conclude that NF-IL-6 is a critical transcription factor in mycobacterial control as well as in granulocyte-colony stimulating factor induction resulting in neutrophil activation.

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