The elucidation of the mechanism of interferon gamma mediated xenophagy against intracellular bacteria

2018 Fiscal Year Final Research Report

• 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: Matsuzawa Takeshi 大阪府立大学, 生命環境科学研究科, 准教授 (80370154)
• Project Period (FY): 2015-04-01 – 2019-03-31
• 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

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.

Free Research Field

細菌感染学

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。