A PHOSPHORYLCHOLINE-CONTAINING FILARIAL NEMATODE-SECRETED PRODUCT DISRUPTS B-LYMPHOCYTE ACTIVATION BY TARGETING KEY PROLIFERATIVE SIGNALINGPATHWAYS

Filarial nematodes infect more than 100 million people in the tropics, causing elephantiasis, chronic skin lesions, and blindness, The paras ites are long-lived as a consequence of being able to evade the host i mmune system, but an understanding of the molecular mechanisms underly ing this evasion remains elusive, In this study, we demonstrate that E S-62 (2 mu g/ml), a phosphorylcholine (PC)-containing glycoprotein rel eased by the rodent filarial parasite Acanthocheilonema viteae, is abl e to polyclonally activate certain protein tyrosine kinase and mitogen -activating protein kinase signal-transduction elements in B lymphocyt es. Although this interaction is insufficient to cause B lymphocyte pr oliferation per se, it serves to desensitize the cells to subsequent a ctivation of the phosphoinositide-3-kinase and Ras mitogen-activating protein kinase pathways, and hence also to proliferation, via the Ag r eceptor, The active component of ES-62 appears to be PC, a molecule re cently shown to act as an intracellular signal transducer, as the resu lts obtained with ES-62 are broadly mimicked by PC alone. As PC-contai ning secreted products (PC-ES) are also released by human filarial par asites, our data suggest that PC-ES, by interfering with B cell functi on, could play a role in prolonging filarial infection in parasitized individuals.