Pseudomonas aeruginosa eliminates natural killer cells via phagocytosis-induced apoptosis.
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.
Chung
Jin Woong
JW
Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea.
Piao
Zheng-Hao
ZH
Yoon
Suk Ran
SR
Kim
Mi Sun
MS
Jeong
Mira
M
Lee
Suk Hyung
SH
Min
Jeong Ki
JK
Kim
Jae Wha
JW
Cho
You-Hee
YH
Kim
Jin Chul
JC
Ahn
Jeong Keun
JK
Kim
Kyoon Eon
KE
Choi
Inpyo
I
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
D053453:Caspase 9; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; C506434:Casp9 protein, mouse