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This article will review the known factors which are host derived or borne out of the interaction between Borrelia burgdorferi and the cells of the various organ systems in order to understand the process of infection B. burgdorferi as an arthropod-borne pathogen must adapt to various and diverse environments in its life cycle. In the invertebrate vector, this organism must tolerate the conditions of the tick midgut as well as the conditions after systemic dissemination. In the vertebrate host, this organism which resides initially in the skin, spreads hematogenously to the heart, brain, joints, and possibly to other tissues as well. At each site of infection, this organism must survive to induce the chronic course of illness characteristic of
Lyme borreliosis. Evidence will be presented for the adhesion of B. burgdorferi to cells of diverse origins which suggests that the initiation of cellular injury may lack specificity. Other host non-specific responses will be reviewed.