title: Glucose depletion in the airway surface liquid is essential for sterility of the airways.
abstract: Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources--including glucose--in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Pezzulo
authors.forename: Jeydith
authors.initials: J
authors.lastname: Gutiérrez
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Duschner
authors.forename: Kelly S
authors.initials: KS
authors.lastname: McConnell
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Taft
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ernst
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Yahr
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.forename: Julia
authors.initials: J
authors.lastname: Klesney-Tait
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
mesh_terms: D000818:Animals; D001826:Body Fluids; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D011550:Pseudomonas aeruginosa; D020545:Respiratory Mucosa / Q000378:metabolism / Q000382:microbiology*; D012137:Respiratory System / Q000382:microbiology; D013242:Sterilization
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; C430746:SLC2A10 protein, human; D005947:Glucose