Activation of human monocytic cells by Borrelia burgdorferi and Treponema pallidum is facilitated by CD14 and correlates with surface exposure of spirochetal lipoproteins

Here we examined the involvement of CD14 in monocyte activation by motile B orrelia burgdorferi and Treponema pallidum. B, burgdorferi induced secretio n of IL-8 by vitamin D-3-matured THP-1 cells, which was inhibited by a CD14 -specific mAb known to block cellular activation by LPS and the prototypic spirochetal lipoprotein, outer surface protein A. Enhanced responsiveness t o B, burgdorferi also was observed when THP-1 cells were transfected with C D14, Because borreliae within the mammalian host and in vitro-cultivated or ganisms express different lipoproteins, experiments also were performed wit h "host-adapted') spirochetes grown within dialysis membrane chambers impla nted into the peritoneal cavities of rabbits. Stimulation of THP-1 cells by host-adapted organisms was CD14 dependent and, interestingly, was actually greater than that observed with in vitro-cultivated organisms grown at eit her 34 degrees C or following temperature shift from 23 degrees C to 37 deg rees C, Consistent with previous findings that transfection of Chinese hams ter ovary cells with CD14 confers responsiveness to LPS but not to outer su rface protein A, B, burgdorferi failed to stimulate CD14-transfected Chines e hamster ovary cells, T, pallidum also activated THP-1 cells in a CD14-dep endent manner, although its stimulatory capacity was markedly less than tha t of B, burgdorferi. Moreover, cell activation by motile T, pallidum was co nsiderably less than that induced by treponemal sonicates. Taken together, these findings support the notion that lipoproteins are the principle compo nent of intact spirochetes responsible for monocyte activation, and they in dicate that surface exposure of lipoproteins is an important determinant of a spirochetal pathogen's proinflammatory capacity.