Ascaris suum-derived products induce human neutrophil activation via a G protein-coupled receptor that interacts with the interleukin-8 receptor pathway

Infection with tissue migrating helminths is frequently associated with int ense granulocyte infiltrations. Several host-derived factors are known to m ediate granulocyte recruitment to the tissues, but less attention has been paid to how parasite-derived products trigger this process. Parasite-derive d chemotactic factors which selectively recruit granulocytes have been desc ribed, but nothing is known about which cellular receptors respond to these agents. The effect of products from the nematodes Ascaris suum, Toxocara c anis, and Anisakis simplex on human neutrophils were studied. We monitored four parameters of activation: chemotaxis, cell polarization, intracellular Ca2+ transients, and priming of superoxide anion production. Body fluids o f A. suum (ABF) and T. canis (TcBF) induced strong directional migration, s hape change, and intracellular Ca2+ transients. ABF also primed neutrophils for production of superoxide anions. Calcium mobilization in response to A . suum-derived products was completely abrogated by pretreatment,vith pertu ssis toxin, implicating a classical G protein-coupled receptor mechanism in the response to ABF. Moreover, pretreatment with interleukin-8 (IL-8) comp letely abrogated the response to ABF, demonstrating desensitization of a co mmon pathway. However, ABF was unable to fully desensitize the response to IL-8, and binding to CXCR1 or CXCR2 was excluded in experiments using RBL-2 H3 cells transfected with the two human IL-8 receptors. Our results provide the first evidence for a direct interaction between a parasite-derived che motactic factor and the host's chemotactic network, via a novel G protein-c oupled receptor which interacts with the IL-8 receptor pathway.