| Project/Area Number |
16590373
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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 |
Bacteriology (including Mycology)
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| Research Institution | Toho University |
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Principal Investigator |
MIYAZAKI Shuichi Faculty of Medicine, Associate Professor, 医学部, 助教授 (30120314)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | H. influenzae / Gr-1highPMN / IL-15 / NK cell / BBB / intracellular parasite / H.influenzae / PM / Gr-1^<high> / PMN / neutrophil / subset / meningitis / blood brain barrier / Gr-1 / CD25 / CD80 |
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| Research Abstract |
Polymorphonuclear leukocytes (PMNs) can be divided into Gr-1^<high> and Gr-1^<low> subpopulations, but the differences in the functions of these cells in the host are unknown. This study investigated the roles of these two cell populations in the clearance of an intracellular pathogen (Haemophilus influenzae) causing murine peritonitis and pneumonia. Microarray analysis and quantitative real time-PCR analysis of proteose peptone-elicited peritoneal murine PMNs showed that IL-15 mRNA levels were significantly higher in Gr-1^<high> PMNs than in Gr-1^<low> PMNs. In addition, IL-15 was produced only by Gr-1-positive PMNs, especially Gr-l^<high> PMNs. IL-15 was required for efficient clearance of experimental murine H. influenzae pneumonia, as four days post-infection lungs from IL-15 knockout mice contained 50-100 fold more bacteria than did wild type mouse lungs. Gr-1-PMN depleted C57BL/6 mice were more susceptible to H. influenzae pneumonia than were Gr-1-PMN replete C57BL/6 mice or C57BL/6 nude mice, demonstrating that Gr-1-PMNs are important in the clearance of intracellular bacteria. IL-15-activated natural killer (NK) cells killed H. influenzae in PMNs. Flow cytometry confirmed the expression of CD69 on the cell membrane of IL-15-activated NK cells. Our results show that Gr-l^<high> PMNs produce more IL-15 and that IL-15-activated NK cells protect against early infection by H. influenzae.
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