Disruption of nuclear factor-interleukin-6, a transcription factor, results in severe mycobacterial infection.
Nuclear factor-interleukin-6 (NF-IL-6) is one of several nuclear transcription factors (NF-IL-6, NF-kappaB, PU.1, interferon-regulatory factor 1, Egr-1, and Stat-1). NF-IL-6 and NF-kappaB 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-gamma, tumor necrosis factor-alpha, 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.
Sugawara
I
I
Department of Molecular Pathology, The Research Institute of Tuberculosis, Kiyose, Tokyo, Japan. sugawara@jata.or.jp
Mizuno
S
S
Yamada
H
H
Matsumoto
M
M
Akira
S
S
D000818:Animals; D015169:Colony Count, Microbial; D016207:Cytokines / Q000235:genetics; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D016898:Interferon-alpha / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009164:Mycobacterium Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D016898:Interferon-alpha; D015850:Interleukin-6; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma