Borrelia burgdorferi BBB07 interaction with integrin ?3?1stimulates production of pro-inflammatory mediators in primary human chondrocytes

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Abstract
Borrelia burgdorferi, the causative agent of Lyme disease, activates multiple signalling pathways leading to induction of pro-inflammatory mediators at sites of inflammation. Binding of B. burgdorferi to integrin α3β1 on human chondrocytes activates signalling leading to release of several pro-inflammatory mediators, but the B. burgdorferi protein that binds integrin α3β1 and elicits this response has remained unknown. A search of the B. burgdorferi genome for a canonical integrin binding motif, the RGD (Arg–Gly–Asp) tripeptide, revealed several candidate ligands for integrins. In this study we show that one of these candidates, BBB07, binds to integrin α3β1 and inhibits attachment of intact B. burgdorferi to the same integrin. BBB07 is expressed during murine infection as demonstrated by recognition by infected mouse sera. Recombinant purified BBB07 induces pro-inflammatory mediators in primary human chondrocyte cells by interaction with integrin α3β1. This interaction is specific, as P66, another integrin ligand of B. burgdorferi, does not activate signalling through α3β1. In summary, we have identified a B. burgdorferi protein, BBB07, that interacts with integrin α3β1 and stimulates production of pro-inflammatory mediators in primary human chondrocyte cells.