The bacterial quorum-sensing molecule, N-3-oxo-dodecanoyl-L-homoserine lactone, inhibits mediator release and chemotaxis of murine mast cells.

Abstract

Bacterial colonization relies on communication between bacteria via so-called "quorum-sensing molecules", which include the acyl-homoserine lactone group. Certain acyl-homoserine lactones can modulate mammalian cell function and are thought to contribute to bacterial pathogenicity. Given the role of mast cells in host defense, we investigated the ability of acyl-homoserine lactones to modulate mast cell function. We utilized murine primary mast cell cultures to assess the effect of acyl-homoserine lactones on degranulation and cytokine release in response to different stimuli. We also assessed cell migration in response to chemoattractants. The effect of acyl-homoserine lactones in vivo was tested using a passive cutaneous anaphylaxis model. Two of the tested quorum-sensing molecules, N-3-oxo-dodecanoyl-L-homoserine lactone and N-Dodecanoyl-L-homoserine lactone, inhibited IgE dependent and independent degranulation and mediator release from primary mast cells. Further testing of N-3-oxo-dodecanoyl-L-homoserine lactone, the most potent inhibitor and a product of Pseudomonas aeruginosa, revealed that it also attenuated chemotaxis and LPS induced cytokine production. In vivo, N-3-oxo-dodecanoyl-L-homoserine lactone inhibited the passive cutaneous anaphylaxis response in mice. The ability of N-3-oxo-dodecanoyl-L-homoserine lactone to stabilize mast cells may contribute to the pathogenicity of P. aeruginosa but could potentially be exploited therapeutically in allergic disease.