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

Linda K Bockenstedt1, Alexia A Belperron1, Jialing Mao1

  • 1Dept of Internal Medicine, Section of Rheumatology, Allergy and Immunology, Yale School of Medicine, New Haven, CT, United States.

Insights

Researchers developed a mouse model for Borrelia miyamotoi infection, an emerging tick-borne relapsing fever. This model aids in studying B. miyamotoi pathogenesis and disease, offering insights into tick-borne illnesses.

Area of Science:

  • Medical Entomology
  • Infectious Diseases
  • Pathogen Biology

Background:

  • Borrelia miyamotoi is an emerging relapsing fever spirochete transmitted by Ixodes ticks.
  • Ixodes ticks also transmit Lyme disease agents, highlighting the importance of understanding B. miyamotoi.
  • An established animal model for B. miyamotoi infection and pathology was previously lacking.

Purpose of the Study:

  • To develop and characterize a laboratory mouse model for Borrelia miyamotoi infection.
  • To investigate the pathogenesis and host immune response to B. miyamotoi using this model.
  • To assess the potential for reinfection in mice that have cleared B. miyamotoi.

Main Methods:

  • Infection of mice (wild-type, Myd88-/-, Rag1-/-, and splenectomized) via needle inoculation and tick-mouse transmission using a clinical B. miyamotoi isolate (CT14D4).
  • Monitoring for spirochetemia, bacterial clearance, and host pathology.
  • Genomic analysis of the B. miyamotoi isolate.
  • Histopathological examination of infected organs.

Main Results:

  • A reproducible mouse model for B. miyamotoi infection was established, supporting both needle inoculation and tick-borne transmission.
  • Relapsing spirochetemia was observed in wild-type, Myd88-/-, and splenectomized mice, with eventual clearance.
  • Rag1-/- mice exhibited persistent bacteremia, indicating the role of adaptive immunity in controlling B. miyamotoi.
  • Cleared infections conferred resistance to reinfection in wild-type mice.
  • Histopathology revealed extramedullary hematopoiesis and inflammatory infiltrates, particularly in the liver and brain of Rag1-/- mice.

Conclusions:

  • The developed mouse model is effective for studying Borrelia miyamotoi infection, pathogenesis, and host-pathogen interactions.
  • The model facilitates research into hard-tick relapsing fever and associated diseases.
  • Findings highlight the importance of the adaptive immune response in controlling B. miyamotoi infections.

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