Diverse Lyme disease spirochete species evade restriction by human complement

Disseminated human Lyme borreliosis (LB) is traditionally associated with invasive spirochete species from the Borrelia burgdorferi sensu lato (s.l.) complex. The Borrelia burgdorferi sensu lato complex consists of 23 spirochete species worldwide, with additional species being proposed. Interactions between the host immune system and Borrelia species have been studied for a diverse range of vertebrate reservoirs of LB spirochetes, including lizards and snakes, as well as the widely recognized rodent and bird reservoirs. Humans are the vertebrate species most susceptible to B. burgdorferi s.l. spirochetes, as demonstrated by the increasing number of diagnosed LB cases worldwide. However, few studies have evaluated differences in the borreliacidal action of human complement against specific Borrelia species. Using the serum sensitivity test, we analyzed whether complement-mediated killing of 10 spirochete species from the B. burgdorferi s.l. complex varies among healthy human individuals of different ages and sexes. Our results show that the 10 genospecies exhibit varying sensitivities to human complement and can be classified into three statistically distinct groups: high, medium, and low sensitivity. Complement sensitivity did not correlate with the known human health impact of these genospecies; similar resistance to the killing effects of human serum was found among Borrelia species that are major causes of LB worldwide and species with unclear pathogenicity to humans. Additionally, females showed reduced complement-mediated Borrelia killing compared to males for all Borrelia species in almost all age groups. Age and biological sex interacted for the Borrelia species most sensitive to human complement. Overall, the effectiveness of complement-mediated killing of the different Borrelia species tended to decrease with age, with more complex age-dependent changes observed for some Borrelia species.