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

Abstract

The Lyme disease spirocheteBorrelia burgdorferidrives a range of acute and chronic maladies in humans and other incidental hosts infected with the pathogen. However, a primary vertebrate reservoir,Peromyscus leucopusappears spared from any symptomology following infection. This has led to a common assumption 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 largely unknown. Here we compared infection ofP. leucopuswithB. burgdorferiwith infection of the traditionalB. burgdorferimurine models—C57BL/6J and C3H/HeNMus musculus, which develop signs of inflammation akin to human disease. We find that in contrast to our expectations,B. burgdorferiwere able to reach much higher burdens inM. musculus, and that the overall kinetics of infection differed between the two rodent species. Surprisingly, 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. These observations provide new insight into the nature of reservoir species and theB. burgdorferienzootic cycle.Author SummaryThe bacteria that causes 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 and find contrary to expectationsB. burgdorferiappear to colonize its natural host worse than conventional lab mouse models. 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.