The NKG2D-activating receptor mediates pulmonary clearance of Pseudomonas aeruginosa.
The NKG2D-activating receptor is expressed on cytotoxic lymphocytes and interacts with ligands expressed on the surface of cells stressed by pathogenic and nonpathogenic stimuli. In this study, we investigated the physiologic importance of NKG2D receptor-ligand interactions in response to acute pulmonary Pseudomonas aeruginosa infection. P. aeruginosa infection increased the expression of mouse NKG2D ligands (Rae1) in airway epithelial cells and alveolar macrophages in vivo and also increased the cell surface expression of human NKG2D ligands (ULBP2) on airway epithelial cells in vitro. NKG2D receptor blockade with a specific monoclonal antibody inhibited the pulmonary clearance of P. aeruginosa. NKG2D receptor blockade also resulted in decreased production of Th1 cytokines and nitric oxide in the lungs of P. aeruginosa-infected mice. Additionally, NKG2D receptor blockade reduced the epithelial cell sloughing that accompanies P. aeruginosa infection. Macrophage phagocytosis and bronchoalveolar lavage cellularity were not different in P. aeruginosa-infected mice with and without NKG2D receptor blockade. These results demonstrate the importance of NKG2D-mediated immune activation in the clearance of acute bacterial infection and suggest that epithelial cell-lymphocyte interactions mediate pulmonary cytokine production, epithelial cell integrity, and bacterial clearance.
Borchers
Michael T
MT
Department of Environmental Health, Division of Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA. michael.borchers@uc.edu
Harris
Nathaniel L
NL
Wesselkamper
Scott C
SC
Zhang
Shiping
S
Chen
Yi
Y
Young
Lisa
L
Lau
Gee W
GW
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D008024:Ligands; D008168:Lung / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011971:Receptors, Immunologic / Q000502:physiology*; D055607:Receptors, Natural Killer Cell; D014132:Trachea / Q000382:microbiology
D016207:Cytokines; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D009569:Nitric Oxide