The uptake of a Klebsiella pneumoniae capsule polysaccharide mutant triggers an inflammatory response by human airway epithelial cells.
The means by which airway epithelial cells sense a bacterial infection and which intracellular signalling pathways are activated upon infection are poorly understood. A549 cells and human primary airway cells (NHBE) were used to investigate the response to infection with Klebsiella pneumoniae. Infection of A549 and NHBE with K. pneumoniae 52K10, a capsule polysaccharide (CPS) mutant, increased the surface levels of ICAM-1 and caused the release of IL-8. By contrast, the wild-type strain did not elicit these responses. Consistent with a functional role for these responses, there was a correlation between ICAM-1 levels and the number of adherent leukocytes on the epithelial cell surface. In addition, treatment of neutrophils with IL-8 enhanced their ability to kill K. pneumoniae. Strain 52K10 was internalized by A549 cells more efficiently than the wild-type, and when infections with 52K10 were performed in the presence of cytochalasin D the inflammatory response was abrogated. These findings suggest that cellular activation is mediated by bacterial internalization and that CPS prevents the activation through the blockage of bacterial adhesion and uptake. Collectively, the results indicate that bacterial internalization by airway epithelial cells could be the triggering signal for the activation of the innate immune system of the airway. Infection of A549 cells by 52K10 was shown to trigger the nuclear translocation of NF-kappaB. Evidence is presented showing that 52K10 activated IL-8 production through Toll-like receptor (TLR) 2 and TLR4 pathways and that A549 cells could use soluble CD14 as TLR co-receptor.
Regueiro
Verónica
V
Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS), Palma de Mallorca, Spain.|Unidad de Investigación, Hospital Universitario Son Dureta, Andrea Doria 55, 07014 Palma Mallorca, Spain.
Campos
Miguel A
MA
Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS), Palma de Mallorca, Spain.|Unidad de Investigación, Hospital Universitario Son Dureta, Andrea Doria 55, 07014 Palma Mallorca, Spain.
Pons
Jaume
J
Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS), Palma de Mallorca, Spain.|Servicio de Inmunología, Hospital Universitario Son Dureta, Andrea Doria 55, 07014 Palma Mallorca, Spain.
Albertí
Sebastián
S
Área de Microbiología, Departamento de Biología, Universidad de las Islas Baleares, Palma de Mallorca, Spain.|Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS), Palma de Mallorca, Spain.
Bengoechea
José A
JA
Institut Universitari d'Investigacions en Ciències de la Salut (IUNICS), Palma de Mallorca, Spain.|Unidad de Investigación, Hospital Universitario Son Dureta, Andrea Doria 55, 07014 Palma Mallorca, Spain.
D002214:Capsules; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007711:Klebsiella pneumoniae / Q000378:metabolism* / Q000502:physiology; D011134:Polysaccharides / Q000378:metabolism* / Q000494:pharmacology; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D002214:Capsules; D011134:Polysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018799:Intercellular Adhesion Molecule-1