Comparative reservoir competence of inbredPeromyscus leucopus, C57BL/6J, and C3H/HeN forBorrelia burgdorferiB31

Abstract

AbstractThe Lyme disease spirocheteBorrelia burgdorfericauses a range of acute and chronic maladies in humans and other incidental hosts infected with the pathogen. However, a primary vertebrate reservoir,Peromyscus leucopus, is reported not to have reduced fitness following infection. One hypothesis for this observation is thatP. leucopusandB. burgdorferiexist symbiotically:P. leucopusrestrain their immune response against the microbe and enable the enzootic cycle whileB. burgdorferiavoids causing damage to the host. While aspects of this hypothesis have been tested, the exact interactions that occur betweenP. leucopusandB. burgdorferiduring infection remain understudied. Here we compared infection ofP. leucopuswithB. burgdorferiB31 with infection of the traditionalB. burgdorferimurine models—C57BL/6J and C3H/HeNMus musculus, which develop signs of inflammation akin to human disease. We find thatB. burgdorferiwere able to reach much higher burdens inM. musculus, and that the overall kinetics of infection differed between the two rodent species. We also found thatP. leucopusremained infectious to larvalIxodes scapularisfor a far shorter period than eitherM. musculusstrain. In line with these observations, we found thatP. leucopusdoes launch a modest but sustained inflammatory response againstB. burgdorferiin the skin, which we hypothesize leads to reduced bacterial viability and infectivity in these hosts. Similarly, we also observe evidence of inflammation in infectedP. leucopushearts. These observations provide new insight into reservoir species and theB. burgdorferienzootic cycle.Author SummaryThe bacteria that cause Lyme disease,Borrelia burgdorferi, must alternate between infecting a vertebrate host—usually rodents or birds—and ticks. In order to be successful in that endeavor the bacteria must avoid being killed by the vertebrate host before it can infect a new larval tick. In this work we examine howB. burgdorferiand one of its primary vertebrate reservoirs,Peromyscus leucopus, interact during an experimental infection. We find thatB. burgdorferiappear to colonize its natural host less successfully than conventional laboratory mouse models which aligns with a sustained seemingly anti-bacterial response byP. leucopusagainst the microbe. These data question long-held assumptions aboutP. leucopusimmunology and could potentially serve as a foundation to uncover ways to disrupt the spread ofB. burgdorferiin nature.