title: Pseudomonas aeruginosa-derived rhamnolipids subvert the host innate immune response through manipulation of the human beta-defensin-2 expression.
abstract: Pseudomonas aeruginosa is a well-known cause of infections especially in compromised patients. To neutralize this pathogen, the expression of antimicrobial factors in epithelial cells is crucial. In particular the human beta-defensin hBD-2 is especially active against P. aeruginosa. In this study, we identified rhamnolipids in P. aeruginosa culture supernatants that are able to prevent the pathogen-induced hBD-2 response in keratinocytes. The presence of rhamnolipids within the host cells and inhibition assays suggest that calcium-regulated pathways and protein kinase C activation are impaired by rhamnolipids. In consequence, the induction of hBD-2 in keratinocytes by P. aeruginosa-derived flagellin as well as the host's own hBD-2 mediator interleukin IL-1β is inhibited. Strikingly, rhamnolipids did not affect the release of the proinflammatory mediator interleukin IL-8 by flagellin. Thus, in addition to their function in establishment and persistence of P. aeruginosa infections, rhamnolipids can be engaged by P. aeruginosa for a targeted attenuation of the innate immunity to manage its survival and colonization on compromised epithelia.
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: Jomtje
authors.initials: J
authors.lastname: Dössel
authors.forename: Ulf
authors.initials: U
authors.lastname: Meyer-Hoffert
authors.forename: Jens-Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gerstel
mesh_terms: D002478:Cells, Cultured; D005408:Flagellin / Q000276:immunology; D006017:Glycolipids / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D053583:Interleukin-1beta / Q000378:metabolism; D015603:Keratinocytes / Q000382:microbiology; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity*; D023083:beta-Defensins / Q000096:biosynthesis*
chemical_list: C106641:DEFB4A protein, human; D006017:Glycolipids; D053583:Interleukin-1beta; D023083:beta-Defensins; C418382:rhamnolipid; D005408:Flagellin; D011493:Protein Kinase C