title: Pseudomonas aeruginosa eliminates natural killer cells via phagocytosis-induced apoptosis.
abstract: Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes the relapse of illness in immunocompromised patients, leading to prolonged hospitalization, increased medical expense, and death. In this report, we show that PA invades natural killer (NK) cells and induces phagocytosis-induced cell death (PICD) of lymphocytes. In vivo tumor metastasis was augmented by PA infection, with a significant reduction in NK cell number. Adoptive transfer of NK cells mitigated PA-induced metastasis. Internalization of PA into NK cells was observed by transmission electron microscopy. In addition, PA invaded NK cells via phosphoinositide 3-kinase (PI3K) activation, and the phagocytic event led to caspase 9-dependent apoptosis of NK cells. PA-mediated NK cell apoptosis was dependent on activation of mitogen-activated protein (MAP) kinase and the generation of reactive oxygen species (ROS). These data suggest that the phagocytosis of PA by NK cells is a critical event that affects the relapse of diseases in immunocompromised patients, such as those with cancer, and provides important insights into the interactions between PA and NK cells.
authors.affiliation: Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea.
authors.forename: Jin Woong
authors.initials: JW
authors.lastname: Chung
authors.forename: Zheng-Hao
authors.initials: ZH
authors.lastname: Piao
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Mira
authors.initials: M
authors.lastname: Jeong
authors.forename: Suk Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Jeong Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
authors.forename: You-Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Jin Chul
authors.initials: JC
authors.lastname: Kim
authors.forename: Jeong Keun
authors.initials: JK
authors.lastname: Ahn
authors.forename: Kyoon Eon
authors.initials: KE
authors.lastname: Kim
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053453:Caspase 9 / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008545:Melanoma / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010587:Phagocytosis / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D053453:Caspase 9; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; C506434:Casp9 protein, mouse