D3258: Parasitic nematode fatty acid and retinol binding proteins alter fly immunity

Parasitic nematodes can manipulate their hosts’ immune systems through the release of excretory/secretory products which function to aid in nematode survival while causing damage to the host. One protein commonly found in the ESPs of nematodes is fatty acid and retinol binding proteins (FARs). In order to elucidate the role of FARs our laboratory developed the first insect model for characterizing the immunomodulatory effects of FARs in vivo and found that certain FARs deplete lipid signaling precursors in vivo as well as in vitro, and modulate immunity in Drosophila melanogaster. Our results show that two FARs from insect parasite Steinernema carpocapsae Sc-FAR-1 and Sc-FAR-2 dampen D. melanogaster immunity including key components of the immune response including the phenoloxidase cascade and antimicrobial peptide production. Furthermore, a FAR from the free-living Caenorhabditis elegans and the hookworm Ancylostoma ceylanicum dampen fly immunity, decreasing resistance to infection. Surprisingly, a FAR from intestinal murine nematode Heligmosomoides polygyrus has shown to elicit no immunomodulatory effects in D. melanogaster and does not affect the outcome of survival against bacterial infection. In vitro competition assay with various fatty-acids show Hp-FAR-2 exhibit a preference for oleic acid and Sc-FAR-1 and Sc-FAR-2 exhibit a preference for linoleic acid. These results suggest that FARs elicit their immunomodulatory effects by altering the availability of lipid signaling molecules necessary for an efficient immune response and may explain why some FARs elicit immunomodulatory effects as opposed to others. Our findings characterize various FARs from four different parasites using D. melanogaster.