Project/Area Number |
15K08469
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Bacteriology (including mycology)
|
Research Institution | Osaka Prefecture University |
Principal Investigator |
|
Project Period (FY) |
2015-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | 細胞内寄生菌 / 自然免疫 / 細胞自律的免疫 / マクロファージ / インターフェロン / オートファジー / 細菌感染学 / ゼノファジー |
Outline of Final Research Achievements |
Professional phagocytes, such as macrophages, have a specialized apparatus for use against invading pathogens. After phagocytosis, pathogens are eliminated by these phagocytes. Intracellular bacteria have survival strategies that interfere with the bactericidal ability of phagocytes. Interferon-γ (IFN-γ) is a potent macrophage activator, and stimulation by this cytokine is critical for cell-autonomous innate immunity against intracellular bacteria. Our group has previously demonstrated that autophagy, a host degradation system, is activated by IFN-γ, and this action contributes to IFN-γ-mediated innate immunity. Here, we characterized the IFN-γ-mediated selective autophagy against Listeria monocytogenes, and these phenotypes are consistent with LC3-associated phagocytosis (LAP), which has recently emerged as an innate immune response that is related to autophagy. We therefore conclude that LAP is mobilized for IFN-γ-mediated cell-autonomous innate immunity.
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Academic Significance and Societal Importance of the Research Achievements |
選択的オートファジーは損傷ミトコンドリアの排除等、生体の恒常性維持の観点からだけではなく、細菌を含む病原細菌の感染防御や腫瘍細胞の駆除等、生体防御の観点からも重要である。IFN-γによる選択的オートファジーの活性化メカニズムの一端を解明した本研究は、オートファジーがどのようにして選択性・特異性を上昇させているのかを理解する一助となる。以上のことから本研究により、細菌感染症学領域だけではなく細胞生物学領域における新たな知見が得られたと考えられる。
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