title: Borrelia burgdorferi BBB07 interaction with integrin alpha3beta1 stimulates production of pro-inflammatory mediators in primary human chondrocytes.
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 alpha(3)beta(1) on human chondrocytes activates signalling leading to release of several pro-inflammatory mediators, but the B. burgdorferi protein that binds integrin alpha(3)beta(1) 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 alpha(3)beta(1) 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 alpha(3)beta(1). This interaction is specific, as P66, another integrin ligand of B. burgdorferi, does not activate signalling through alpha(3)beta(1). In summary, we have identified a B. burgdorferi protein, BBB07, that interacts with integrin alpha(3)beta(1) and stimulates production of pro-inflammatory mediators in primary human chondrocyte cells.
authors.affiliation: Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Boston, MA, USA.
authors.forename: Aruna K
authors.initials: AK
authors.lastname: Behera
authors.forename: Enrique
authors.initials: E
authors.lastname: Durand
authors.forename: Carla
authors.initials: C
authors.lastname: Cugini
authors.forename: Styliani
authors.initials: S
authors.lastname: Antonara
authors.forename: Lori
authors.initials: L
authors.lastname: Bourassa
authors.forename: Ethan
authors.initials: E
authors.lastname: Hildebrand
authors.forename: Linden T
authors.initials: LT
authors.lastname: Hu
authors.forename: Jenifer
authors.initials: J
authors.lastname: Coburn
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000502:physiology*; D018925:Chemokines / Q000096:biosynthesis; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D008024:Ligands; D008193:Lyme Disease / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000032:analysis; D015398:Signal Transduction