Human Complement Evasion Is Widespread Among Lyme Borreliosis Spirochete Species

Disseminated human Lyme borreliosis is primarily associated with invasive spirochetes from the Borrelia burgdorferi sensu lato complex. Host-Borrelia interactions have been studied in a diverse range of vertebrate reservoirs. But despite the key role of the complement system in innate immunity, comparative studies evaluating the susceptibility of individual Borrelia species to human complement-mediated killing are limited. Using serum sensitivity assays, we analyzed complement-mediated killing of 10 B. burgdorferi s.l. genospecies in healthy individuals of different ages and sexes. The tested genospecies showed markedly different sensitivities to human complement. Statistical clustering divided the genospecies into three distinct groups based on whether their sensitivity to human complement was high, medium, or low. Complement resistance did not correlate with the recognized pathogenicity of the genospecies; species with unclear pathogenic potential exhibited resistance levels comparable to the major species causing human Lyme borreliosis, B. burgdorferi sensu stricto, B. afzelii and B. garinii. Females generally showed reduced complement-mediated killing compared to males. In addition, complement activity tended to decline with age, identifying host age and biological sex as important factors influencing the human innate immune response against Borrelia. Our findings suggest that the ability to evade human complement may be more widespread among Borrelia species than previously assumed. These results support an emerging model in which complement-mediated selection may shape host associations and transmission success without serving as an absolute predictor of Borrelia virulence.