Phagocytic Entry of Legionella pneumophila into Macrophages through Phosphatidylinositol 3,4,5-Trisphosphate-Independent Pathway
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概要
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Legionella pneumophila, a causative agent of Legionnaire’s disease, is an intracellular pathogen. It intervenes in the signal transduction of macrophages by secreting effector molecules through the Icm/Dot type IV secretion system (T4SS). There is a connection between signaling cascades that regulate phagocytosis and the production of reactive oxygen species (ROS). Class I phosphatidylinositol 3-kinase (PI3-K) and its product phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) play key roles in the reorganization of cytoskeleton (phagocytosis) and activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (ROS production). We investigated the production of PI(3,4,5)P3 and recruitment of class I PI3-K and Rac1 during phagocytosis of L. pneumophila by macrophages. Transient recruitment of class I PI3-K as well as PI(3,4,5)P3 production was observed around a phagocytosed T4SS mutant LELA3118 or avirulent mutant 25D in an early stage of infection. In contrast, class I PI3-K was recruited while accumulation of PI(3,4,5)P3 was not observed around wild type JR32. Immunoglobulin G (IgG)-opsonized live JR32, which would activate class I PI3-K through the Fcγ receptor pathway, did not induce PI(3,4,5)P3 production. Regardless of whether wild type or mutants were used, transient Rac1 accumulation was observed around bacteria. These results indicate that the phagocytosis of wild type L. pneumophila occurs via a special mechanism in which PI(3,4,5)P3 production is absent. This suggests that L. pneumophila may inhibit the production of PI(3,4,5)P3, but not the recruitment of class I PI3-K and Rac1, in a T4SS-dependent manner. L. pneumophila may start the modulation of host signaling cascade immediately after contact with host cells to evade the ROS-dependent bactericidal system while completing entry into macrophages.
著者
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Tanikawa Takashi
Laboratory of Microbiology and Immunology and the Global COE Program, University of Shizuoka School
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Imai Yasuyuki
Laboratory Of Microbiology And Immunology And Coe Program In The 21st Century University Of Shizuoka
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Miyake Masaki
Laboratory Of Microbiology And Immunology And The Global Coe Program School Of Pharmaceutical Scienc
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Harada Toshihiko
Laboratory Of Microbiology And Immunology And The Global Coe Program School Of Pharmaceutical Scienc
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Iwasaki Yasunori
Laboratory of Microbiology and Immunology and The Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka
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Yamada Masao
Laboratory of Microbiology and Immunology and The Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka
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Harada Toshihiko
Laboratory of Microbiology and Immunology and The Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka
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Tanikawa Takashi
Laboratory of Microbiology and Immunology and COE Program in the 21st Century, University of Shizuoka School of Pharmaceutical Sciences
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