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Borrelia miyamotoi infection negatively impacts pregnancy outcomes in immunodeficient mice
Alexia A Belperron1, Jialing Mao1, Carmen J Booth2
1Department of Internal Medicine, Section of Rheumatology, Allergy and Immunology, Yale School of Medicine, New Haven, CT, United States.
Introduction:
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.
Methods:
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.
Results:
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.
Discussion:
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.
Insights
Hard tick relapsing fever (RF) infection with Borrelia miyamotoi adversely affects pregnancy outcomes in immunodeficient mice, reducing pup survival. Unlike soft tick RF, Borrelia miyamotoi did not infect embryos directly, suggesting distinct pregnancy impacts.
Area of Science:
- Microbiology
- Immunology
- Reproductive Biology
Background:
- Soft tick relapsing fever (RF) infections are known to cause adverse pregnancy outcomes.
- The impact of hard tick RF on pregnancy remains largely unknown.
- Borrelia miyamotoi is a hard tick-borne bacterium.
Purpose of the Study:
- To assess the impact of Borrelia miyamotoi infection on pregnancy outcomes in a mouse model.
- To compare the effects of hard tick RF with known soft tick RF outcomes during pregnancy.
Main Methods:
- Utilized a mouse model of hard tick RF using Borrelia miyamotoi (CT14D4).
- Assessed litter sizes, pup survival, and spirochetemia in pups from immunodeficient (Rag1-/-) and wild-type (WT) dams.
- Infection was administered via needle inoculation or tick transmission before and after mating.
Main Results:
- Immunodeficient dams infected with Borrelia miyamotoi showed reduced live pup delivery and survival rates.
- Tick-transmitted infection resulted in more embryonic deaths than live births, with spirochetes found in placentae but not embryos.
- Pregnant infected mice developed more severe anemia compared to non-pregnant mice.
Conclusions:
- Borrelia miyamotoi infection adversely affects fetal viability and pup survival in immunodeficient mice.
- Embryos from infected dams did not harbor spirochetes, indicating a difference from soft tick-borne relapsing fever.
- These findings highlight distinct pregnancy outcomes between hard and soft tick-borne relapsing fever infections.
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