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

Abstract

The spirochetal bacterium Borrelia recurrentis causes louse-borne relapsing fever (LBRF). B. recurrentis is unique because, as opposed to other Borrelia spirochetes, this strictly human pathogen is transmitted by lice. Despite the high mortality and historically proven epidemic potential and current outbreaks in African countries and Western Europe, research on LBRF has been obstructed by the lack of suitable animal models. The previously used grivet monkey model is associated with ethical concerns, among other issues. An existing immunodeficient mouse model does not limit bacteremia due to its impaired immune system. In this study, we used genetically diverse Collaborative Cross (CC) lines to develop the first LBRF immunocompetent mouse model. Out of 12 CC lines tested, CC046 mice consistently developed B. recurrentis-induced spirochetemia during the first 3 days postchallenge as concordantly detected by dark-field microscopy, culture, and quantitative PCR. However, spirochetemia was not detected from day 4 through day 10 postchallenge. The high-level spirochetemia (>107 cells/ml of blood) observed in CC046 mice was similar to that recorded in LBRF patients as well as immunocompetent mouse strains experimentally infected by tick-borne relapsing fever (RF) spirochetes, Borrelia hermsii and Borrelia persica. In contrast to the Old World and New World RF spirochetes, which develop multiple relapses (n = 3 to 9), B. recurrentis produced only single culture-detectable spirochetemia in CC046 mice. The lack of relapses may not be surprising, as LBRF patients and the grivet monkey model usually develop no or only 1 to 2 spirochetemic relapses. The novel model will now allow scientists to study B. recurrentis in the context of intact immunity.