CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-kappa B translocation | Academic Article individual record
abstract

Immune cells are activated during cellular responses to antigen by two described mechanisms: (i) direct uptake of antigen and (ii) extraction and internalization of membrane components from antigen-presenting cells. Although endocytosis of microbial antigens by pattern recognition molecules (PRM) also activates innate immunity, it is not known whether this involves extraction and internalization of microbial surface components. Epithelial cells on mucosal surfaces use a variety of receptors that are distinct from the classical endocytic PRM to bind and internalize intact microorganisms. Nonclassical receptor molecules theoretically could act as a type of endocytic PRM if these molecules could recognize, bind, extract, and internalize a pathogen-associated molecule and initiate cell signaling. We report here that the interaction between the cystic fibrosis transmembrane conductance regulator (CFTR) and the outer core oligosaccharide of the lipopolysaccharide (LPS) in the outer membrane of Pseudomonas aeruginosa satisfies all of these conditions. P. aeruginosa LPS was specifically recognized and bound by CFTR, extracted from the organism's surface, and endocytosed by epithelial cells, leading to a rapid (5- to 15-min) and dynamic translocation of nuclear transcription factor NF-kappa B. Inhibition of epithelial cell internalization of P. aeruginosa LPS prevented NF-kappa B activation. Cellular activation depended on expression of wild-type CFTR, because both cultured Delta F508 CFTR human airway epithelial cells and lung epithelial cells of transgenic-CF mice failed to endocytose LPS and translocate NF-kappa B. CFTR serves as a critical endocytic PRM in the lung epithelium, coordinating the effective innate immune response to P. aeruginosa infection.

author list (cited authors)
Schroeder, T. H., Lee, M. M., Yacono, P. W., Cannon, C. L., Gerceker, A. A., Golan, D. E., & Pier, G. B.
publication date
2002
keywords
  • Pseudomonas Aeruginosa
  • Mice, Inbred C3H
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Lipopolysaccharides
  • Cell Membrane
  • Lipid Bilayers
  • Respiratory Mucosa
  • Biological Transport
  • Cell Line
  • Humans
  • NF-kappa B
  • Mice
  • Animals
  • Epithelial Cells
altmetric score

3.0

citation count

108

PubMed Central ID
11997458
identifier
88281SE
Digital Object Identifier (DOI)
start page
6907
end page
6912
volume
99
issue
10