PLoS Pathogens (Aug 2009)

Pseudomonas aeruginosa eliminates natural killer cells via phagocytosis-induced apoptosis.

  • Jin Woong Chung,
  • Zheng-Hao Piao,
  • Suk Ran Yoon,
  • Mi Sun Kim,
  • Mira Jeong,
  • Suk Hyung Lee,
  • Jeong Ki Min,
  • Jae Wha Kim,
  • You-Hee Cho,
  • Jin Chul Kim,
  • Jeong Keun Ahn,
  • Kyoon Eon Kim,
  • Inpyo Choi

DOI
https://doi.org/10.1371/journal.ppat.1000561
Journal volume & issue
Vol. 5, no. 8
p. e1000561

Abstract

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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.