Diego Cadavid1, Edwin Garcia, Harald Gelderblom. 1. Department of Neurology and Neuroscience and the Center for the Study of Emerging Pathogens, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA. cadavidi@umdnj.edu
Abstract
BACKGROUND: Relapsing fever (RF) is a multisystemic spirochetal infection caused by different Borrelia species. Studies in our laboratory have shown that disease severity varies depending on the infecting serotype. However, the relative contribution of each serotype to pathogenesis during mixed infections is not known. To investigate this, we compared the outcome of infection with isogenic serotypes 1 (Bt1) or 2 (Bt2) of the RF agent B. turicatae alone or in combination. METHODS: B cell-deficient mice were used for these experiments, to avoid serotype clearance by the host's variable membrane protein-specific antibodies. Observers masked to infection status examined infected and uninfected control mice for clinical disease and functional impairment for up to 65 days. RESULTS: All mice developed persistent infection with the serotypes with which they were originally inoculated. Severe vestibular dysfunction developed in mice infected with Bt1 alone and was associated with increased morbidity and mortality. However, coinfection with Bt2 significantly reduced the severity of vestibular dysfunction and prevented earlier mortality. In contrast, coinfection with Bt1 had little effect on the severe arthritis caused by Bt2 infection. CONCLUSIONS: The manifestations of infection with B. turicatae are significantly influenced by the combination of serotypes present during mixed infection.
BACKGROUND: Relapsing fever (RF) is a multisystemic spirochetal infection caused by different Borrelia species. Studies in our laboratory have shown that disease severity varies depending on the infecting serotype. However, the relative contribution of each serotype to pathogenesis during mixed infections is not known. To investigate this, we compared the outcome of infection with isogenic serotypes 1 (Bt1) or 2 (Bt2) of the RF agent B. turicatae alone or in combination. METHODS: B cell-deficient mice were used for these experiments, to avoid serotype clearance by the host's variable membrane protein-specific antibodies. Observers masked to infection status examined infected and uninfected control mice for clinical disease and functional impairment for up to 65 days. RESULTS: All mice developed persistent infection with the serotypes with which they were originally inoculated. Severe vestibular dysfunction developed in miceinfected with Bt1 alone and was associated with increased morbidity and mortality. However, coinfection with Bt2 significantly reduced the severity of vestibular dysfunction and prevented earlier mortality. In contrast, coinfection with Bt1 had little effect on the severe arthritis caused by Bt2 infection. CONCLUSIONS: The manifestations of infection with B. turicatae are significantly influenced by the combination of serotypes present during mixed infection.