Differential acquired immune responsiveness to bacterial lipoproteins in Lyme disease‐resistant and ‐susceptible mouse strains

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Abstract
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‐γ than did cells from C57BL/6J mice. Cells from uninfected mice did not respond. No TNF‐α or IL‐1β 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‐γ, 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‐γ 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.