Pseudomonas aeruginosa Eliminates Natural Killer Cells via Phagocytosis-Induced Apoptosis

被引:27
作者
Chung, Jin Woong [1 ,2 ]
Piao, Zheng-Hao [1 ,3 ]
Yoon, Suk Ran [1 ]
Kim, Mi Sun [1 ]
Jeong, Mira [1 ,4 ]
Lee, Suk Hyung [1 ,4 ]
Min, Jeong Ki [5 ]
Kim, Jae Wha [6 ]
Cho, You-Hee [7 ]
Kim, Jin Chul [8 ]
Ahn, Jeong Keun [8 ]
Kim, Kyoon Eon [3 ]
Choi, Inpyo [1 ,4 ]
机构
[1] Korea Res Inst Biosci & Biotechnol, Cell Therapy Res Ctr, Taejon, South Korea
[2] Dong A Univ, Dept Biol Sci, Pusan, South Korea
[3] Chungnam Natl Univ, Dept Biochem, Coll Nat Sci, Taejon, South Korea
[4] Univ Sci & Technol, Dept Funct Genom, Taejon, South Korea
[5] Korea Res Inst Biosci & Biotechnol, Antibody Therapy Res Ctr, Taejon, South Korea
[6] Korea Res Inst Biosci & Biotechnol, Genome Res Ctr, Taejon, South Korea
[7] Sogang Univ, Dept Life Sci, Coll Nat Sci, Seoul, South Korea
[8] Chungnam Natl Univ, Dept Microbiol, Sch Biosci & Biotechnol, Taejon, South Korea
关键词
NEUTROPHIL APOPTOSIS; HOST-DEFENSE; NK CELL; INFECTIONS; BACTEREMIA; CLEARANCE; PYOCYANIN; MACROPHAGES; RESISTANCE; EXPRESSION;
D O I
10.1371/journal.ppat.1000561
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:14
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