The complement system is one of the major innate defense mechanisms Borrelia burgdorferi sensu lato has to overcome to establish an infection of mammalian hosts and to cause Lyme borreliosis in humans. Borrelia prevents complement-mediated killing during host colonization through (i) recruitment of host complement regulators by Borrelia, (ii) evasion mechanisms by Borrelia itself, and (iii) exploitation of tick proteins by Borrelia. These interactions with complement can be host species-specific. This review provides an overview of interactions between Borrelia, tick, and host leading to evasion of complement-mediated killing.
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