The First Immunocompetent Mouse Model of Strictly Human Pathogen, Borrelia recurrentis

Area of Science:

• Infectious Diseases
• Microbiology
• Immunology

Background:

• Louse-borne relapsing fever (LBRF) is caused by Borrelia recurrentis, a human pathogen transmitted by lice.
• Existing animal models for LBRF research are limited, with ethical concerns or inability to replicate key disease aspects.
• A lack of suitable immunocompetent models hinders understanding of B. recurrentis pathogenesis and host immunity.

Purpose of the Study:

• To develop the first immunocompetent mouse model for studying LBRF.
• To utilize genetically diverse Collaborative Cross (CC) lines to identify a suitable host for Borrelia recurrentis infection.
• To enable research on B. recurrentis within the context of an intact immune system.

Main Methods:

• Testing 12 genetically diverse Collaborative Cross (CC) mouse lines for susceptibility to Borrelia recurrentis.
• Inoculating mice and monitoring for spirochetemia using dark-field microscopy, culture, and quantitative PCR.
• Comparing spirochetemia levels and relapse patterns with human LBRF cases and other relapsing fever spirochetes.

Main Results:

• CC046 mice consistently developed B. recurrentis-induced spirochetemia within the first 3 days post-challenge.
• High-level spirochetemia (>10^7 cells/ml) in CC046 mice mirrored levels seen in LBRF patients.
• Unlike other relapsing fever spirochetes, B. recurrentis induced only a single spirochetemic episode in CC046 mice, aligning with human LBRF clinical presentation.

Conclusions:

• CC046 mice represent the first immunocompetent model for louse-borne relapsing fever.
• This novel model allows for the investigation of Borrelia recurrentis infection under intact immunity.
• The model's characteristics closely resemble human LBRF, offering significant advantages for future research.