Interkingdom communication: understanding how mast cells translate and respond to bacterial quorum sensing signals

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Many species of bacteria communicate with each other through a cell density dependent signaling system, termed quorum sensing. These signals are mediated by small hormone-like molecules and allow a population of bacteria to co-ordinate their gene expression and activities. It is becoming evident that certain components of the quorum sensing system can also influence the behavior of eukaryotic cells. Of particular interest is the emerging data suggesting that a certain class of quorum sensing molecules produced by gram-negative bacteria, acyl homoserine lactones (AHL), can modulate mammalian immune responses. Preliminary data from my laboratory indicate that certain AHL inhibit mast cell responses to bacterial components and antigen without influencing cell viability. Mast cells play an important role in host defense, acting as sentinels of the immune system, strategically located at sites that interface with our external environment. They are rapidly activated in response to bacterial infection, and can be crucial for the early recruitment of effector cells such as neutrophils. Thus the mast cell is a highly relevant target cell in which to study this poorly understood form of inter-kingdom communication that likely plays an important role in mediating both detrimental and beneficial interactions between mammals and their microbiota. The experiments proposed in this application will examine AHL mediated regulation of mast cell function by; 1) determining the influence of AHL on mast cell activity, 2) delineating mast cell signaling pathways modulated by AHL, 3) identifying potential mammalian receptors for AHL.