E-039. Effects of Sand Fly Salivary Component Maxadilan on Murine Dendritic Cell Migration In Vitro

K. E. Pauken, W. Wheat, R. Titus;
Colorado State Univ., Fort Collins, CO.

Vector-borne diseases such as leishmaniasis are a significant world health issue. The etiological agents of leishmaniasis are protozoan parasites of the genus Leishmania, which are transmitted by phlebotomine sand flies. Successful transmission of parasites such as L. major from arthropods to mammalian hosts require vector salivary components that modulate host immune responses ensuring parasitic entry, survival and resulting pathogenesis. One such component is the peptide maxadilan (MAX) derived from sand fly (L. longipalpis) saliva. Evidence has emerged showing that MAX alters several aspects of murine dendritic cells (DCs). Migration of antigen-primed DCs from the site of vector-mediated parasite inoculation to secondary lymphoid organs is essential to initiation of an adaptive immune response. We sought to determine whether MAX modulates anti-leishmanial immunity by impeding the course of epithelial DC migration to draining lymph nodes. This work has shown that MAX treatment of LPS-stimulated murine bone-marrow derived DCs prevents optimal up-regulation of the chemokine receptor CCR7. We hypothesize that phenotypically altered DCs fail to adequately mobilize to T cell areas of draining lymph nodes, stalling the initiation of adaptive immune responses against leishmanial antigens. Transwell tissue culture chambers were utilized to simulate migration in vitro: DC migration was facilitated through the membrane by supplementation with CCR7 chemokine ligands CCL19 and CCL21. Using this approach, we show that MAX treatment resulted in significantly reduced numbers of migrating cells, suggesting that reduced surface expression of CCR7 correlates with decreased migration. Comparable results were obtained using DCs derived from either an L. major-resistant (C3H) or -susceptible (BALB/c) murine strain. These data suggest that MAX modulates migration from the epithelium to the secondary lymphoid organs, a critical step in successfully eliminating L. major parasites.