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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Pseudomonas aeruginosa eliminates natural killer cells via phagocytosis-induced apoptosis
Jin Woong Chung1, Zheng-Hao Piao, Suk Ran Yoon
1Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea.
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.
Insights
Pseudomonas aeruginosa (PA) invades natural killer (NK) cells, causing their death and promoting tumor metastasis. Restoring NK cell numbers can mitigate this PA-induced metastasis, offering insights into immunocompromised patient relapse.
Area of Science:
- Immunology
- Microbiology
- Oncology
Background:
- Pseudomonas aeruginosa (PA) is an opportunistic pathogen causing severe illness and relapse in immunocompromised individuals.
- NK cells are crucial for immune surveillance against pathogens and cancer.
Purpose of the Study:
- To investigate the interaction between PA and NK cells.
- To elucidate the mechanisms by which PA affects NK cell function and impacts tumor metastasis.
Main Methods:
- Transmission electron microscopy to visualize PA internalization into NK cells.
- Assessment of NK cell apoptosis pathways (PI3K, caspase 9, MAP kinase, ROS).
- In vivo studies of tumor metastasis and the effect of NK cell adoptive transfer.
Main Results:
- PA invades NK cells, inducing phagocytosis-induced cell death (PICD).
- PA infection augments tumor metastasis and reduces NK cell numbers in vivo.
- Adoptive transfer of NK cells mitigated PA-induced metastasis.
- PA invasion involves PI3K activation, leading to caspase 9-dependent apoptosis via MAP kinase and ROS.
Conclusions:
- PA phagocytosis by NK cells is a critical mechanism contributing to disease relapse in immunocompromised patients, particularly cancer patients.
- Understanding PA-NK cell interactions provides insights into immune evasion strategies of opportunistic pathogens.
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