Origin, kinetics of circulation and fatein vivoof the major excretory–secretory product ofAcanthocheilonema viteae

Abstract

The excretions-secretions (E-S) of Acanthocheilonema viteae consist mainly of one product, molecular weight 62kDa. This molecule is synthesized during the vertebrate phase of the parasite life-cycle and is first detectable in the E-S of L4 parasites. It is cross-reactive with E-S of human filarial parasites as a consequence of possessing a phosphorylcholine (PC) moiety. The 62 kDa molecule has been employed as a model for the study of the origin and fate of filarial E-S. Immunohistological analysis has shown the molecule to be located predominantly in the parasite gut. Transplantation of adult female [35S] methionine pulsed worms into uninfected jirds resulted in the radio-labelled secreted 62 kDa antigen being detected in the bloodstream within 4 h by SDS-PAGE/immunoprecipitation analysis. The systemic half-life of the molecule as estimated by clearance of injected, purified 125I-labelled material was measured in naive and infected jird hosts. It was reduced from 2-7 h in naive animals to less than 30 min in 4-10 week infected rodents, a finding which correlated with clearance of antigen by antibody in the infected group. In animals infected for longer time periods the serum half-life returned to the values observed in naive jirds. The idea that this change in half-life may reflect differences in the nature of 62 kDa antigen containing circulating immune complexes as infection progresses is discussed. The 125I-labelled antigen is predominantly removed from the circulation via the liver and ultimately excreted in the urine in a non-antigenic form. This work provides the first description of the origin, kinetics of circulation and fate of a defined filarial E-S product and may aid in determining the function and assessing the diagnostic utility of PC-bearing E-S components.

In vitroproduction and characterization of excretory/secretory products ofOnchocerca volvulus

“…Titanji* Parasite, 1997, 4, 351-358 of the cuticle (Haque & Capron, 1986). Some of these ESP have been found to be biologically active molecules such as enzymes (Harnett et al, 1989) which aid in the migration of these tissue-dwelling parasites through host tissues. By virtue of their direct contact with the host immune system, they may also persistently stimulate the host immune system, causing local inflammatory responses (Maizels et al, 1982;Ottessen, 1984;Philipp étal, 1988).…”

A Filarial Nematode-Secreted Phosphorylcholine-Containing Glycoprotein Uncouples the B Cell Antigen Receptor from Extracellular Signal-Regulated Kinase-Mitogen-Activated Protein Kinase by Promoting the Surface Ig-Mediated Recruitment of Src Homology 2 Domain-Containing Tyrosine Phosphatase-1 and Pac-1 Mitogen-Activated Kinase-Phosphatase

“…Of particular interest, filarial nematodes have been shown to secrete glycoproteins containing a known immunomodulator, phosphorylcholine (PC) (2,4). We have demonstrated that the PC moiety of one such molecule, ES-62, a glycoprotein that is a major ES of the rodent filarial parasite Acanthocheilonema viteae (5) and has homologues in human filarial nematodes, inhibits Ag receptor-driven B and T cell proliferation by selectively uncoupling the Ag receptors from key downstream proliferative signaling pathways (4, 6 -10). Thus, although ES-62-mediated inhibition of lymphocyte activation is not targeted against the early Ag receptor-coupled phospholipase C (PLC-␥)-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate, it selectively down-regulates certain protein kinase C isoforms and desensitizes protein tyrosine kinase-dependent coupling of the Ag receptors to the phosphatidylinositol 3-kinase and the Ras-ErkMAP kinase signaling cascades (6 -9).…”

Presence of Phosphorylcholine on a Filarial Nematode Protein Influences Immunoglobulin G Subclass Response to the Molecule by an Interleukin-10-Dependent Mechanism

“…ES-62 is a secreted PC-containing glycoprotein of the rodent filarial nematode Acanthocheilonema viteae (11). Subcutaneous injection of this parasite product into BALB/c mice results in the generation of high levels of immunoglobulin G1 (IgG1) antibody, but virtually no IgG2a, directed against the non-PC epitopes of the molecule (8).…”

“…Groups of four 6-to 8-week-old female BALB/c mice were given a total of four subcutaneous injections of purified parasite material (3 g per injection), each 1 week apart. Serum samples were collected at day 0 and day 35 and stored at Ϫ20°C until assayed by enzyme-linked immunosorbent assay (ELISA) (11).…”