Establishment of a laboratory mouse model to study Borrelia miyamotoi infection and disease.

Borrelia miyamotoi is an emerging relapsing fever spirochete transmitted by Ixodes spp. ticks that serve as vectors for other human pathogens, including the agents of Lyme disease. To date, an animal model to study tick-borne B. miyamotoi infection and pathology has not been reported. Here, we describe the development of a laboratory mouse model of infection using clinical isolate CT14D4 derived from the blood of a Connecticut resident with disseminated Lyme disease. Genomic analysis revealed that the CT14D4 genome was similar to other B. miyamotoi strains isolated from Ixodes scapularis ticks in the eastern United States. We show that CT14D4 can be propagated in mice by needle inoculation and through a tick-mouse infection cycle. Relapsing spirochetemia was observed in wild-type (WT), Myd88 -/-, and splenectomized mice, all of which eventually cleared the infections. In contrast, Rag1 -/- mice lacking B and T cells remain persistently bacteremic. WT mice that had cleared CT14D4 infection are resistant to reinfection with this B. miyamotoi strain. Spirochetes were visualized in several organs after perfusion fixation of infected Rag1 -/- mice, including the brain, with histopathology revealing extramedullary hematopoiesis and inflammatory infiltrates that were most pronounced in the liver. WT mice exhibited similar but milder pathology during periods of bacteremia. These studies provide a useful model to study hard-tick relapsing fever pathogenesis and disease.