Relative importance of STAT4 in murine tuberculosis.
This study was designed to determine the roles of STAT proteins in defence against mycobacterial infection. Airborne infection of STAT4 knockout (KO) mice with a Mycobacterium tuberculosis strain induced large granulomas with massive neutrophil infiltration over time, while that in STAT6 KO mice did not. The STAT4 KO mice succumbed to mycobacterial infection by the 80th day after infection. Compared with the levels in wild-type (WT) and STAT6 KO mice, pulmonary inducible nitric oxide synthase, interferon-alpha, -beta and -gamma mRNA levels were significantly lower in STAT4 KO mice, but expression of interleukin-2, -6, -12 and -18 mRNAs was slightly higher up to the fifth week after aerial infection. Therefore, STAT4, but not STAT6, appears to be a critical transcription factor in mycobacterial regulation.
Sugawara
I
I
Department of Molecular Pathology, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-0022, Japan.
Yamada
H
H
Department of Molecular Pathology, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-0022, Japan.
Mizuno
S
S
Department of Molecular Pathology, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-0022, Japan.
D000818:Animals; D015169:Colony Count, Microbial; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006099:Granuloma / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D013154:Spleen / Q000382:microbiology; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D019001:Nitric Oxide Synthase