Filarial nematode AsnRS interacts with interleukin 8 receptors in iDCs but causes different gene expression patterns compared to iDCs stimulated by interleukin 8.

Nematode derived substances are known to down regulate host immune responses in order to survive in the human host. Brugia malayi is a parasitic nematode responsible for long lasting and disabling infection known as lymphatic filariasis in humans. The therapeutic benefit of a controlled parasitic nematode infection on the course of inflammatory bowel disease (IBD) has been demonstrated in both animal and human models. However the inability of individual purified nematode proteins to recreate this beneficial effect has limited the application of component immunotherapy to human disease. This experiment addresses the hypothesis that the genes regulated by IL8 and recombinant Brugia malayi AsnRS (rBmAsnRS) are different even though it is known that both molecules interact with IL-8 receptors. Furthermore, we theorize that the signal transduction pathways activated by IL-8 and rBmAsnRS are different because it is known that the extracellular G protein loops utilized by IL-8 and rBmAsnRS to activate IL8 receptors, are different. These results obtained with a single recombinant nematode protein, rBmAsnRS, share immunological features with those observed in a whole nematode infection and include desirable features for treatment of idiopathic inflammatory diseases, such as IBD.

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Kron MA, Metwali A, Vodanovic-Jankovic S, Elliott D