Comparative transcriptome analysis of and C3H mice infected with the Lyme disease pathogen.

Unlabelled: Lyme disease (LD), the most prevalent tick-borne disease of humans in the Northern Hemisphere, is caused by the spirochetal bacterium of () sensu lato complex. In nature, spirochetes are continuously transmitted between ticks and mammalian or avian reservoir hosts. mice are considered the primary mammalian reservoir of in the United States. Earlier studies demonstrated that experimentally infected mice do not develop disease. In contrast, C3H mice, a widely used laboratory strain of in the LD field, develop severe Lyme arthritis. To date, the exact tolerance mechanism of mice to -induced infection remains unknown. To address this knowledge gap, the present study has compared spleen transcriptomes of and C3H/HeJ mice infected with strain 297 with those of their respective uninfected controls. Overall, the data showed that the spleen transcriptome of -infected mice was much more quiescent compared to that of the infected C3H mice. To date, the current investigation is one of the few that have examined the transcriptome response of natural reservoir hosts to infection. Although the experimental design of this study significantly differed from those of two previous investigations, the collective results of the current and published studies have consistently demonstrated very limited transcriptomic responses of different reservoir hosts to the persistent infection of LD pathogens.

Importance: The bacterium () causes Lyme disease, which is one of the emerging and highly debilitating human diseases in countries of the Northern Hemisphere. In nature, spirochetes are maintained between hard ticks of spp. and mammals or birds. In the United States, the white-footed mouse, , is one of the main reservoirs. In contrast to humans and laboratory mice (e.g., C3H mice), white-footed mice rarely develop clinical signs (disease) despite being (persistently) infected with . How the white-footed mouse tolerates infection is the question that the present study has attempted to address. Comparisons of genetic responses between -infected and uninfected mice demonstrated that, during a long-term infection, C3H mice reacted much stronger, whereas mice were relatively unresponsive.