Borrelia miyamotoi infection negatively impacts pregnancy outcomes in immunodeficient mice.

Soft tick relapsing fever (RF) infections cause adverse pregnancy outcomes, but the impact of hard tick RF on pregnancy is unknown. We assessed pregnancy outcomes in a mouse model of hard tick RF using the Borrelia miyamotoi clinical isolate CT14D4. Litter sizes, pup survival and presence of spirochetemia were assessed in pups from immunodeficient (Rag1-/-) dams infected by needle inoculation or tick transmission both before and after mating, and from wild type (WT) dams infected by needle inoculation prior to breeding. Outcomes of pregnancies in immunodeficient mice revealed reduced numbers of live pups delivered and/or pup survival to weaning, independent of the route of infection, in comparison with uninfected dams. With tick-transmitted infection, we assessed the number of viable fetal-placental units present at embryonic gestation day 18.5 and found higher numbers of embryonic pups than live pups delivered in a similarly infected group of dams followed to term. Spirochetes were not detected in blood or tissues from day 18.5 embryos but were found within yolk sacs and placentae. Infection in weanling mice from immunodeficient dams was rare regardless of timing or route of infection of the dams, and likely due to spirochetes transmitted during delivery, not in utero. Complete blood cell counts performed at various time points after infection revealed that infection led to anemia which was more severe in pregnant mice. In contrast to immunodeficient mice, the pup survival rate in WT mice infected by needle inoculation with CT14D4 prior to pregnancy was high. Low levels of B. miyamotoi-specific antibodies were detected in weaned pups, which may be of maternal origin. Our results demonstrate that Borrelia miyamotoi infection has adverse effects on fetal viability and pup survival in immunodeficient Rag1-/- mice. Embryos, however, did not harbor spirochetes and the majority of pups borne from infected dams were not infected, revealing differences between hard and soft tick-RF infections outcomes during murine pregnancy.