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Department of Cell Biology Faculty
Haseeb A. Siddiqi, Ph.D.
Departments of Cell Biology, Pathology and Medicine, College of Medicine, and School of Public Health
Tel: (718) 270-1610 • Fax: 718-270-2656
Host-parasite interactions and mechanisms of pathogenesis and immunity in schistosomiasis; reproductive biology of schistosomes and mechanisms of chemoattraction in schistosome males and females.
Schistosomiasis is a chronic granulomatous disease which afflicts 200 to 300 million people worldwide and causes 500,000 to 1,000,000 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 demonstrated 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 the chemoattractant plays any role in induction of sexual maturation in developing females and whether females continue to express the chemoreceptor following mating.
Treatment of schistosome females with soybean agglutinin (SBA) effectively blocks their attraction to males or their excretory-secretory products, and chemoattraction is restored in n-acetyl-D-galactosamine (GalNAc) - treated females. We have also demonstrated competitive binding of SBA and anti-GP50 mAb to the schistosome tegument. These observations suggest that GalNAc-containing receptors, possibly GP50, the major SBA-binding schistosome glycan, mediate chemoreception in schistosome females. These findings may explain the observed differences in morbidity between individuals with different blood groups. Individuals with blood group B or O may afford protection because of their natural anti-A or by mounting a more efficient antibody response directed against GalNAc-containing structures shared by blood group A red blood cells.
We have also demonstrated that elevated tumor necrosis factor α (TNFα) levels in murine schistosomiasis are associated with oviposition and circumoval granuloma formation, and that the newly-formed circumoval granulomata during the 10 week th post-infection are smaller than those formed earlier, suggesting immune modulation. In addition, TNFα suppresses amino acid uptake and egg production in schistosome females or worm-pairs maintained in vitro.
Director, Clinical Parasitology and Diagnostic Immunology Laboratories, Kings County Hospital Center