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The present study focuses on the role of the biogenic monoamine serotonin (5-hydroxytryptamine) in the biology of sporocyst stages of the human blood fluke, Schistosoma mansoni, and its importance during obligate development within its snail host Biomphalaria glabrata. Based on previous work demonstrating that snails infected with S. mansoni have reduced levels of 5-hydroxytryptamine, we hypothesized that sporocysts actively transport this molecule from the host milieu. Intact sporocysts isolated in vitro take up exogenous 5-hydroxytryptamine via a high-affinity mechanism (K(m)=1.4 micromol l(-1)), and this serotonin transporter-like activity is dependent upon extracellular Na(+) and Cl(-) and is highly sensitive to previously characterized serotonin transporter inhibitors. Autoradiography suggests that transported [(3)H]5-hydroxytryptamine localizes within the body of the sporocyst, and in many cases is found in apical gland cells. Moreover, serotonin transporter-like activity is absent in free-swimming miracidia, the infective stage for the snail host, and the increase in larval serotonin transporter-like activity after miracidium-to-sporocyst transformation is accompanied by a corresponding decrease in steady-state levels of transcripts for tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis. Overall our data suggest that S. mansoni larvae express surface-exposed serotonin transporter-like molecules, and that the transition from free-living miracidium to parasitic mother sporocyst is characterized by an increased dependence upon exogenous 5-hydroxytryptamine.
During murine schistosomiasis, there is a gradual switch from a predominant Th1 cytokine response to a Th2-dominated response after egg laying, an event that favors the formation of granuloma around viable eggs. Egg-derived glycoconjugates, including glycolipids, may play a crucial role in this phenomenon. In this study, we used a model of dendritic cell sensitization to study the role of egg glycoconjugates in the induction of specific immune response to soluble egg Ag (SEA) and to investigate the possibility that CD1d, a molecule implicated in glycolipid presentation, may be involved in such a phenomenon. We show that, when captured, processed, and presented to naive T lymphocytes by dendritic cells, egg, but not larval, Ag skew the immune response toward a Th2 response. Periodate treatment reversed this effect, indicating that the sugar moiety of SEA is important in this phenomenon. Using DC treated ex vivo with a neutralizing anti-CD1d Ab or isolated from CD1d knockout mice, we show that CD1d is crucial in the priming of SEA-specific Th2 lymphocytes. We then evaluated the contribution of CD1d on the development of the SEA-specific immune response and on the formation of the egg-induced liver granuloma during murine schistosomiasis. We find that CD1d knockout mice have a reduced Th2 response after egg laying and develop a less marked fibrotic pathology compared with wild-type mice. Altogether, our results suggest that Ag presentation of parasite glycoconjugates to CD1d-restricted T cells may be important in the early events leading to the induction of Th2 responses and to egg-induced pathology during murine schistosomiasis.
Changes over time in the prevalence and intensity of Schistosoma mansoni infection were measured by serial quantitative stool examinations using the modified Ritchie concentration technique in a 9-year prospective study of an endemic Puerto Rican community with a population of about 1,000 persons. The complete interruption of transmission was achieved by snail control during the 2nd year of the study, in February 1973. Annual stool specimens were obtained from all willing community residents. In addition, from 27 of these residents 10 consecutive stools were collected in each of 3 years: 1973, 1976, 1977. After a chemotherapy campaign with oxamniquine in 1980, only eight of these 27 persons remained untreated. Ten consecutive stools were collected from seven of these untreated individuals in 1981. We calculated the rate of decline (beta) in geometric mean egg count in the cohort of 27 over 5 years and in the subcohort of seven over 9 years. Similarly, beta was calculated from the change in the single annual stool counts in 528 persons providing data for all of the first 6 years of the study. Estimates of the average life-span (-1/beta, in a model assuming constant rate of death) of the adult S. mansoni with 95% confidence intervals are for the cohort of 27, 5.5 years (4.0 to 9.1), for the cohort of seven, 37 years (8.0 to infinity), and and for the cohort of 528, 35 years (16 to infinity).(ABSTRACT TRUNCATED AT 250 WORDS)
Conflicting interpretations regarding the fecundity of schistosomes infecting human beings have arisen and are, in part, due to the inability to directly measure the parameters. The inability to experimentally manipulate human beings necessitates the use of surrogate variables, i.e., number of eggs per gram of feces, as an indicator of worm burden. This study reanalyzes data from quantitative autopsies performed in Egypt by Cheever and colleagues on individuals with active Schistosoma mansoni infections. Exploratory regression analysis of the relationship of female worms recovered to eggs/g of feces and of female worms to eggs retained in host tissues suggests a linear relationship in both cases. Over the observed range of female worms recovered from an individual human being, the estimated worm fecundity, as measured by the number of eggs either in feces or retained in tissues per female worm, is not significantly different from a constant value. Hence, density-dependent fecundity of S. mansoni in the human host, as suggested by others, is not demonstrated in these data.