Natural antibody affects survival of the spirochete Borrelia burgdorferi within feeding ticks

Natural antibodies are those immunoglobulin molecules found in mammalian se rum that arise in the absence of exposure to environmental pathogens and ma y comprise an early host defense against invading pathogens. The spirochete Borrelia burgdorferi first encounters natural antibodies when its arthropo d vector, Ixodes scapularis, begins feeding on a mammalian host. Natural an tibodies may therefore have an impact on pathogens within blood-sucking vec tors, prior to pathogen transmission to the mammal. In this study, we inves tigated whether natural antibodies influenced the number and/or phenotype o f B. burgdorferi organisms within feeding L scapularis nymphs. Using a comp etitive PCR, we found that ticks ingesting a blood meal from B-cell-deficie nt mice, which lack all immunoglobulins, contained fivefold more spirochete DNA than ticks feeding on control mice. Spirochete DNA levels could be red uced to that of controls with passive transfer of normal mouse serum or pol yclonal immunoglobulin M (IgM), but not IgG, into B-cell-deficient mice pri or to placement of infected ticks. At 48 h of tick feeding, 90% of spiroche tes within salivary glands of ticks removed from B-cell-deficient mice were found by confocal immunofluorescence microscopy to express outer surface p rotein A (OspA), compared to only 5% of salivary gland spirochetes from tic ks detached from control mice. Taken together, these results show that inge stion of natural antibodies limits the spirochete burden within feeding tic ks. Because OspA is normally downregulated when spirochetes moved from the tick midgut to the salivary gland, our findings suggest that OspA-expressin g midgut spirochetes may be particularly susceptible to the borrelicidal ef fects of these molecules.