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 Borrelia burgdorferi and Treponema pallidum. B. burgdorferi induced secretion of IL-8 by vitamin D3-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 to B. burgdorferi also was observed when THP-1 cells were transfected with CD14. Because borreliae within the mammalian host and in vitro-cultivated organisms express different lipoproteins, experiments also were performed with "host-adapted" spirochetes grown within dialysis membrane chambers implanted 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 either 34 degrees C or following temperature shift from 23 degrees C to 37 degrees C. Consistent with previous findings that transfection of Chinese hamster ovary cells with CD14 confers responsiveness to LPS but not to outer surface protein A, B. burgdorferi failed to stimulate CD14-transfected Chinese hamster ovary cells. T. pallidum also activated THP-1 cells in a CD14-dependent manner, although its stimulatory capacity was markedly less than that of B. burgdorferi. Moreover, cell activation by motile T. pallidum was considerably less than that induced by treponemal sonicates. Taken together, these findings support the notion that lipoproteins are the principle component of intact spirochetes responsible for monocyte activation, and they indicate that surface exposure of lipoproteins is an important determinant of a spirochetal pathogen's proinflammatory capacity.
Sellati
T J
TJ
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Bouis
D A
DA
Caimano
M J
MJ
Feulner
J A
JA
Ayers
C
C
Lien
E
E
Radolf
J D
JD
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000254:growth & development / Q000276:immunology*; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology; D006224:Cricetinae; D015194:Diffusion Chambers, Culture; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008074:Lipoproteins / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D008567:Membranes, Artificial; D051379:Mice; D008809:Mice, Inbred C3H; D017551:Microdialysis; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D011817:Rabbits; D014162:Transfection; D014210:Treponema pallidum / Q000276:immunology* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018950:Lipopolysaccharide Receptors; D008074:Lipoproteins; D008567:Membranes, Artificial; C072045:OspA protein; D002762:Cholecalciferol