UNDERLYING MECHANISMS OF SCHISTOSOME/SNAIL COMPATIBILITY

点击翻译按钮获取中文摘要

On account of the considerable burden placed on human populations by Schistosoma mansoni in schistosome-endemic areas, an understanding of the basic mechanisms responsible for transmission of these human parasites via their intermediate molluscan hosts is desirable. This research seeks to understand how it is that a miracidium larva is able to penetrate a snail and transform into a sporocyst without eliciting aggressive defensive responses. Since individual snails (Biomphalaria glabrata) may be susceptible or resistant to individual S. mansoni, the cellular and molecular bases for this variability are to be sought. At least some components of this mollusc's internal defense system are subject to modulation by trematode parasites and by stress. Therefore, following treatments proven to modulate hemocyte activity, the influence of such altered states will be evaluated in assays of snail resistance. Assays include in vitro phagocytosis, cytoadherence and cell mediated cytotoxicity, and in vivo resistance to S. mansoni. An hypothesis that the compatibility of schistosome and snail is due in part to mimicry of carbohydrate epitopes will be tested using polyclonal sera, with antigens subjected to proteolytic degradation, and known carbohydrate epitopes used as competing ligands. Substantively improved quantification of in vitro cytotoxicity will allow us to determine whether resistant plasma accelerates sporocyst killing. Another hypothesis implicating lysosomally-derived, plasma enzymes in modulating resistance will be tested both in vivo and in vitro using plasma from appropriately treated snails and defined enzymes. A functional role will be sought for a 50 kD plasma component found uniquely in strains of snail which are resistant to the PR1 strain of S. mansoni. Polyclonal antisera will be used in efforts to block effector functions, and the affinity-purified plasma component will be evaluated for its ability to facilitate recognition and/or cytotoxic hemocyte effector functions. Finally, the relevance of a novel alpha-macroglobulin-like protein in snail plasma to outcomes of snail - schistosome encounters will be investigated.