Pseudomonas aeruginosa-derived rhamnolipids subvert the host innate immune response through manipulation of the human beta-defensin-2 expression.

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.