Pattern of pro-inflammatory cytokine induction in RAW264.7 mouse macrophages is identical for virulent and attenuated Borrelia burgdorferi

摘要

Lyme disease pathogenesis results from a complex interaction between Borrelia burgdorferi and the host immune system. The intensity and nature of the inflammatory response of host immune cells to B. burgdorferi may be a determining factor in disease progression. Gene array analysis was used to examine the expression of genes encoding cytokines, chemokines, and related factors in the joint tissue of infected C3H/HeJ mice and in a murine macrophage-like cell line in response to a disseminating or attenuated clinical isolate of B. burgdorferi. Both isolates elicited a robust pro-inflammatory response in RAW264.7 cells characterized by an increase in transcript levels of genes encoding CC and CXC chemokines, pro-inflammatory cytokines, and TNF superfamily members. Transcription of genes encoding IL-1β, IL-6, MCP-1, MIP-1α, CXCR4 and TLR2 induced in RAW264.7 cells by either live or heat-killed spirochetes did not differ significantly at any time point over a 24-hour period, nor was there a difference in the protein levels of IL-10, TNF-α, IL-6 and IL-12p70 in culture supernatants. Thus, induction of host macrophage expression of pro-inflammatory mediators by host macrophages does not contribute to the differential pathogenicity of different B. burgdorferi strains.