Do white-footed mice, the main reservoir of the Lyme disease pathogen in the United States, clinically respond to the borrelial tenancy?

As white-footed mice, <i>Peromyscus leucopus</i>, are considered the primary animal reservoir of <i>Borreliella burgdorferi sensu stricto</i> (<i>Bb</i>), the main agent of Lyme disease (LD) in the United States, these animals represent the most relevant model to study borrelial spirochetes in the context of their natural life cycle. Previous studies have consistently demonstrated that although white-footed mice respond immunologically to the invasion of the Lyme pathogen, <i>P. leucopus</i> adults do not develop a clinically detectable disease. This tolerance, which is common for mammalian reservoirs of different pathogens, contrasts with detrimental anti-borrelial responses of C3H mice, a widely used animal model of LD, which always result in a clinical manifestation (e.g., arthritis). The current investigation is a follow-up of our recent study that already showed a relative quiescence of the spleen transcriptome for <i>Bb</i>-infected white-footed mice compared to the infected C3H mice. In an effort to identify the mechanism behind this tolerance, in this study, we have evaluated an extensive list of hematological and biochemical parameters measured in white-footed mice after their 70-day-long borrelial infection. Despite missing reference intervals for <i>Peromyscus</i> mice, our sex- and age-matched uninfected controls allowed us to assess the blood and serum parameters. In addition, for our assessment, we also utilized behavioral, immunological, and histological analyses. Collectively, by using the metrics reported herein, the present results have demonstrated clinical unresponsiveness of <i>P. leucopus</i> mice to the borrelial infection, presenting no restriction to a long-term host-pathogen co-existence.