Differential acquired immune responsiveness to bacterial lipoproteins in Lyme disease-resistant and -susceptible mouse strains.
We investigated the effect of Borrelia burgdorferi lipoproteins (outer surface protein A) and the synthetic lipohexapeptide tripalmitoyl-S-glyceryl-Cys-Ser-4(Lys) (Pam3-Cys) on isolated lymph node (LN) cells from Lyme disease-susceptible (C3H/HeJ) and -resistant (C57BL/6J) mice. Mice were either infected with B. burgdorferi for 1 week or left uninfected. Lipoprotein-stimulated LN cells from infected C3H/HeJ mice produced significantly higher levels of the inflammatory cytokines IL-6 and IFN-gamma than did cells from C57BL/6J mice. Cells from uninfected mice did not respond. No TNF-alpha or IL-1beta were produced by LN cells from infected mice of either strain in response to lipoprotein or B. burgdorferi spirochetes. Unlike with IL-6 or IFN-gamma, LN cells from either strain failed to produce IL-10 in response to lipoproteins. However, the LN cells were able to produce this cytokine in response to B. burgdorferi spirochetes or after incubation with phorbol-12-myristate-13-acetate/ionomycin, anti-CD3 antibody alone or anti-CD3 combined with anti-CD28 antibodies. Addition of exogenous IL-10 to lipopeptide-stimulated cultures significantly reduced IFN-gamma and IL-6 production in a dose-dependent fashion. This inhibition was more effective with cells from disease-resistant C57BL/6J mice than with cells from disease-susceptible C3H/HeJ mice. The proclivity to disease of the C3H/HeJ mouse could be simultaneously based on the phenomena of enhanced inflammatory responsiveness to lipoproteins and diminished ability to respond to IL-10. An investigation of the determinants of these two phenomena could be used as a blueprint to elucidate the pathogenesis of Lyme disease in humans.
Ganapamo
Frédéric
F
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
Dennis
Vida A
VA
Philipp
Mario T
MT
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D025065:Borrelia burgdorferi / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D005260:Female; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology; D008074:Lipoproteins / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008074:Lipoproteins; D016753:Interleukin-10