NKG2D is critical for NK cell activation in host defense against Pseudomonas aeruginosa respiratory infection

Scott C. Wesselkamper, Bryan L. Eppert, Gregory T. Motz, Gee W. Lau, Daniel J. Hassett, Michael T. Borchers

Research output: Contribution to journalArticlepeer-review


Pseudomonas aeruginosa is a major cause of nosocomial respiratory infections. The eradication of P. aeruginosa from the lung involves the orchestrated actions of the pulmonary epithelium and both resident and recruited immune cells. The NKG2D receptor is constitutively expressed on the surface of circulating and tissue-resident NK cells (and other cytotoxic lymphocytes), and is capable of controlling NK cell activation and production of cytokines, such as IFN-γ via interactions with ligands expressed on the surface of stressed cells. Previously, we demonstrated that NKG2D mediates pulmonary clearance of P. aeruginosa. In the present study, we investigated the cellular and molecular mechanisms of NKG2D-mediated clearance of P. aeruginosa using a novel transgenic mouse model of doxycycline-inducible conditional expression of NKG2D ligands (retinoic acid early transcript 1, α) in pulmonary epithelial cells. NKG2D ligand expression in this model increased pulmonary clearance, cellular phagocytosis, and survival following P. aeruginosa respiratory infection. Additionally, NK cell sensitivity to ex vivo LPS stimulation was greater in lung cells isolated from naive transgenic mice administered doxycycline. We also showed that NK cells are the primary source of lymphocyte-derived IFN-γ in response to P. aeruginosa respiratory infection. Significantly, we demonstrated that NKG2D is critical to the nonredundant IFN-γ production by pulmonary NK cells following acute P. aeruginosa infection. These results represent the principal report of NKG2D-mediated activation of lung NK cells following respiratory infection with an opportunistic pathogen and further establish the importance of NKG2D in the host response against P. aeruginosa respiratory infection.

Original languageEnglish (US)
Pages (from-to)5481-5489
Number of pages9
JournalJournal of Immunology
Issue number8
StatePublished - 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'NKG2D is critical for NK cell activation in host defense against Pseudomonas aeruginosa respiratory infection'. Together they form a unique fingerprint.

Cite this