| Project/Area Number |
07807063
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nara Medical University |
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Principal Investigator |
KITA Eiji Nara Medical University, Dept.of Bacteriology, Professor, 医学部・細菌学, 教授 (90133199)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Fumiko Nara Medical University, Dept.of Bacteriology, Research Assistant, 医学部, 助手 (70271202)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | tuberculosis / intracellular parasite / L forms / cellular immunity / BCG / 抗酸菌感染症 / マクロファージ / in situ PCR / 免疫維持機構 |
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| Research Abstract |
The present study was done to prove our hypothesis that long-lived acquired resistance of humans to Mycobacterium tuberculosis is ascribed to the transformation of M.tuberculosis into L-form M.tuberculosis in macrophages localized at granulomatous lesions. To determine whether mycobacteria can transform into L forms in vivo, murine BCG infection model was used.
Results obrtained herein were as follows :
1) BCG transformed into L forms in Bcg^r mice after 60 days of infection, and treatment of infected Bcg^s miced with isoniazid (INH) induced the transformation of BCG into L forms.
2) L-form BCG was detected in mononuclear cells of granulomatous lesions in the lung by the in-situ PCR.
3) IFN-gamma was responsible for the transformation of intracellular BCG into L forms.
4) Bcg^s mice immunized with L-form BCG or colonized with L-form BCG were immune from an intravenous infection with a lethal dose of BCG.
5) Reversion of L-form BCG to parental BCG was achieved by treating L form-colonized mice with estrogen or TNF-alpha. This reversion was associated with the enhanced production of TNF-alpha and TGF-beta.
6) In L form-colonized mice, mRNAs for IL-1, IL-12 and IFN-gamma were strongly expressed after an intravenous infection with a lethal dose of BCG.
These data strongly suggest that transformation of BCG into L forms contribute to the maintenance of acquired resistance to infection with a lethal dose of BCG.Such a mechanism is possibly applied to human mycobacterial immunity which can last over a long period.
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