Adaptive immunity in <i>Mus musculus</i> influences the acquisition and abundance of <i>Borrelia burgdorferi</i> in <i>Ixodes scapularis</i> ticks

The Lyme disease spirochete <i>Borrelia burgdorferi</i> cycles between immature black-legged ticks (<i>Ixodes scapularis</i>) and vertebrate reservoir hosts, such as rodents. Larval ticks acquire spirochetes from infected hosts, and the resultant nymphs transmit the spirochetes to naïve hosts. This study investigated the impact of immunocompetence and host tissue spirochete load on host-to-tick transmission (HTT) of <i>B. burgdorferi</i> and the spirochete load inside immature <i>I. scapularis</i> ticks. Wild-type (WT) C57BL/6J mice and mice with severe combined immunodeficiency (SCID) were experimentally infected with <i>B. burgdorferi</i>. To measure HTT, WT and SCID mice were repeatedly infested with <i>I. scapularis</i> larvae, and ticks were sacrificed at three different developmental stages: engorged larvae, 1-month-old, and 12-month-old nymphs. The spirochete loads in immature ticks and mouse tissues were estimated using qPCR. In WT mice, HTT decreased from 90% to 65% over the course of the infection, whereas in the SCID mice, HTT was always 100%. Larvae that fed on SCID mice acquired a much larger dose of spirochetes compared to larvae that fed on WT mice. This difference in spirochete load persisted over tick development where nymphs that fed as larvae on SCID mice had significantly higher spirochete loads compared to their WT counterparts. HTT and the tick spirochete loads were strongly correlated with the mouse tissue spirochete loads. Our study shows that the host immune system (e.g., the presence of antibodies) influences HTT of <i>B. burgdorferi</i> and the spirochete load in immature <i>I. scapularis</i> ticks.IMPORTANCEThe tick-borne spirochete <i>Borrelia burgdorferi</i> causes Lyme disease in humans. This pathogen is maintained in nature by cycles involving black-legged ticks and wildlife hosts. The present study investigated the host factors that influence the transmission of <i>B. burgdorferi</i> from infected hosts to feeding ticks. We infected immunocompetent mice and immunocompromised mice (that cannot develop antibodies) with <i>B. burgdorferi</i> and repeatedly infested these mice with ticks. We determined the percentage of infected ticks and their spirochete loads. This percentage was 100% for immunocompromised mice but decreased from 90% to 65% over time (8 weeks) for immunocompetent mice. The tick spirochete load was much higher in ticks fed on immunocompromised mice compared to ticks fed on immunocompetent mice. In summary, the host immune system influences the transmission of <i>B. burgdorferi</i> from infected hosts to ticks and the spirochete loads in those ticks, which, in turn, determines the risk of Lyme disease for people.