The Immunomodulatory Effects of Ascaris suum Pseudocoelomic Fluid in Th1-Mediated Systems (90.10)

Recent studies found that adoptive transfer of helminth-primed dendritic cells impairs host protection to the enteric pathogen, Citrobacter rodentium. In the present study, we used Ascaris suum pseudocoelomic fluid (PCF) in lieu of infection, and demonstrated that pre-exposure of bone-marrow derived dendritic cells to PCF, prior to LPS stimulation, suppressed activation marker expression and production of IL-12. Similar to LPS, heat-inactivated and extract preparations of C. rodentium induced dendritic cell activation. This activation was suppressed in cells previously exposed to PCF, resulting in decreased expression of CD40, CD86, and MHC II. These findings suggest that PCF may modify Th1 responses in the host. In preliminary studies, BALB/c mice were sensitized with PCF (100 μg), followed by oral inoculation with C. rodentium (2.5 x 10⁸ CFU). Bacterial colonization and colonic hyperplasia was assessed at days 3 and 7 post-infection. Mice receiving two sensitizations prior to inoculation had increased C. rodentium colonization in the cecum and colon by day 7 post-infection, compared to those receiving no pre-treatment. We are currently repeating this experiment using a higher concentration of PCF (200 μg) to enhance differences in bacterial colonization. This model may help determine if PCF alters the course of Th1-mediated immunoregulation in allergic inflammatory responses.