A phosphorylcholine-containing filarial nematode-secreted product disrupts B lymphocyte activation by targeting key proliferative signaling pathways.
Filarial nematodes infect more than 100 million people in the tropics, causing elephantiasis, chronic skin lesions, and blindness. The parasites are long-lived as a consequence of being able to evade the host immune system, but an understanding of the molecular mechanisms underlying this evasion remains elusive. In this study, we demonstrate that ES-62 (2 microg/ml), a phosphorylcholine (PC)-containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, is able to polyclonally activate certain protein tyrosine kinase and mitogen-activating protein kinase signal-transduction elements in B lymphocytes. Although this interaction is insufficient to cause B lymphocyte proliferation per se, it serves to desensitize the cells to subsequent activation of the phosphoinositide-3-kinase and Ras mitogen-activating protein kinase pathways, and hence also to proliferation, via the Ag receptor. The active component of ES-62 appears to be PC, a molecule recently shown to act as an intracellular signal transducer, as the results obtained with ES-62 are broadly mimicked by PC alone. As PC-containing secreted products (PC-ES) are also released by human filarial parasites, our data suggest that PC-ES, by interfering with B cell function, could play a role in prolonging filarial infection in parasitized individuals.
Deehan
M R
MR
Department of Immunology, University of Strathclyde, Glasgow, United Kingdom.
Frame
M J
MJ
Parkhouse
R M
RM
Seatter
S D
SD
Reid
S D
SD
Harnett
M M
MM
Harnett
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004153:Dipetalonema / Q000502:physiology*; D015801:Helminth Proteins / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011817:Rabbits; D013108:Sphingomyelin Phosphodiesterase / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism
D015801:Helminth Proteins; D010767:Phosphorylcholine; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013108:Sphingomyelin Phosphodiesterase; D018631:ras Proteins