Schistosomiasis is a chronic granulomatous disease which afflicts 200 to 300 million people worldwide and causes more than a million deaths annually. Adult schistosomes live in human blood vessels, causing little pathology themselves, and thrive well in the face of a vigorous immune response. Each female lays 300 or more eggs/day depending on the species and the worm burden. When trapped in host tissues the eggs elicit inflammation, and the resultant granulomata form the pathologic basis of schistosomiasis. Since schistosome females do not reach sexual maturity (a requisite for egg production) without mating with males we have been interested in understanding mate-finding mechanisms in schistosomes with the hope that interruption of mate-finding would prevent egg-induced pathology. Using an in vitro bioassay we have learned that developing males elaborate a chemoattractant for females, and that females express a corresponding receptor. Our results suggest that males no longer release the chemoattractant once they are mated. It is not known whether females continue to express the receptor following mating. It is also not known whether the chemoattractant plays any role in induction of sexual maturation in females. The chemoreceptor in females binds a lectin, soybean agglutinin (SBA), suggesting that it contains n-acetyl-D-galactosamine residues. Thus, the possibility of receptor isolation and characterization through lectin-affinity chromatography remains open. We have also demonstrated competitive binding of SBA and anti-GP50 mAb to the schistosome tegument, however, it remains to be determined whether the chemoattractant interferes with binding of SBA or anti-GP50 mAb to the female tegument.

We have also learned that a host-produced molecule, tumor necrosis factor (TNF ), suppresses egg production in schistosome females.Ê Kinetics of TNF production in schistosomiasis (from infection to egg-laying) and a TNF receptor in schistosomes remain to be elucidated.

 

SELECTED PUBLICATIONS

Eveland, L.K. & Haseeb, M.A. 1989. Schistosoma mansoni: Onset of chemoattraction in developing worms. Experientia, 45: 309-310.

Haseeb, M.A. & Eveland, L.K. 1991. Schistosoma mansoni: A chemoattractive factor released by males and its receptor in females. Experientia, 47: 970-974.

Haseeb, M.A., Solomon, W.B. & Palma, J.F. 1996. Schistosoma mansoni: Effect of recombinant tumor necrosis factor alpha on fecundity and [14C]-tyrosine uptake in females maintained in vitro. Comparative Biochemistry & Physiology, 115C(3): 265-269.

Haseeb, M.A. & Craig, J.P. 1997. Suppression of the immune response to diphtheria toxoid in murine schistosomiasis. Vaccine, 15: 45-50.

Haseeb, M.A. 1998. Schistosoma mansoni: Females enhance [14C]-tyrosine incorporation in males maintained in vitro. Journal of Helminthology, 72(2): 123-126.

Haseeb, M.A., Bergquist, N.R., Eveland, L.K. & Eppard, R.C. 1998. Vaccination against schistosomiasis: Progress, prospects and novel approaches. Proceedings of the IX International Congress of Parasitology, 365-372.

Haseeb, M.A., Shirazian, D.J. and Preis, J. 2001. Elevated serum levels of TNF, STNF-RI and sTNF-RII in murine schistosomiasis correlate with schistosome oviposition and circumoval granuloma formation. - in preparation.

 

SUPPORT

Our work is supported by a grant from the World Health Organization.