Seroepidemiology of schistosomiasis in Puerto Rico: evidence for vanishing endemicity.
(17/1591)
The current study summarizes our findings of anti-schistosome egg antibody by the circumoval precipitin test for two different populations in Puerto Rico. One group, exclusively males more than 40 years of age and from all municipalities on the island, was from the Veterans Administration Hospital for the period 1988-1997. The second group resided southeast of San Juan, around the municipality of Caguas and adjacent municipalities east of Caguas, was of both sexes and mostly until 1997 of undetermined ages for the period 1993-1997. Results reveal a yearly decrease in testing requests from the Veterans Administration Hospital from 148 in 1988 and 1989 with 16% positive to three in 1996 through 1998 with none positive. This decrease in testing requests was because of a decrease of suspicion of schistosomiasis in this group. The other patient population from the Caguas region showed a gradual but continuous decrease in seropositive individuals from 21% in 1993 to 12% in 1996, with precipitous decrease to 5% in 1997 and only 1% in 1998. Moreover, there were four patients from which at least two serum samples were obtained one or two years apart and tested. In each instance the more recently obtained sample had lower antibody reactions than the first as reflected in lower percentages of positive egg reactors. The fact that they were treated with praziquantel after the first testing also suggests that the infected population was being eliminated through chemotherapy. These combined results suggest the elimination of infections with Schistosoma mansoni in the traditionally high prevalence regions east of San Juan in the absence of any proactive control efforts in Puerto Rico. Because of the rapid urbanizing of Puerto Rico, the one identifiable control effort is economic development and well being. (+info)
Schistosoma TOR (trispanning orphan receptor), a novel, antigenic surface receptor of the blood-dwelling, Schistosoma parasite.
(18/1591)
Sh-TOR is a novel, putative three transmembrane domain receptor of Schistosoma haematobium, which has no extensive homology to any other known protein. The 0.86 kb open reading frame was found to encode a novel protein, 286 amino acids long and of 32 kDa. It was shown that Sh-TOR can be phosphorylated on tyrosine and the protein sequence reveals a long cytoplasmic tail with several consensus phosphorylation sites for enzymes which characteristically associate with membrane receptors. The proposed topology of Sh-TOR, based on antibody recognition of transfected Sh-TOR, predicts that the amino terminus is extracellular and the carboxyl terminus intracellular. Sh-TOR is a non-glycosylated protein found in the surface tegumental plasma membrane, and tegumental surface pits of adult schistosomes. The 1.35 kb transcript was most highly expressed in the larval stage, which is more susceptible to immune attack. A TOR homologue from Schistosoma mansoni is also described. A homologue from Trypanosoma cruzi, another human parasite was also isolated, but not from the free-living nematode Caenorhabditis elegans. Recombinant Sh-TOR is specifically recognised by a passively protective serum, from baboons vaccinated with irradiated Schistosoma parasite. Together with its surface location, this means that Sh-TOR is also a potential vaccine candidate molecule. (+info)
Isolation of T-cell antigens by using a recombinant protein library and its application to the identification of novel vaccine candidates against schistosomiasis.
(19/1591)
We present here a novel approach to identify T-cell antigens from any infectious agent by use of a library of purified recombinant proteins. Essential features of this strategy include (i) a highly efficient cDNA cloning system which negatively selects against nonrecombinant transformants by making use of the bacterial EcoK restriction system, (ii) affinity staining of cDNA clones expressing recombinant proteins, and (iii) a procedure of simultaneous purification of recombinant proteins from large numbers of isolated clones (representing the protein library) in a single step from pools consisting of up to 24 individual clones. The feasibility of the screening system was confirmed by constructing a protein library of the human parasite Schistosoma mansoni. The recombinant antigens of this library were used to stimulate CD4(+) T cells derived from the axillary lymph nodes of mice vaccinated with irradiated cercariae. In initial screening experiments, we detected parasite-specific proliferation and gamma interferon (IFN-gamma) secretion in response to several pools of cDNA clones. Further analysis of one particular pool revealed that only one of its constituents stimulated considerable IFN-gamma secretion by CD4(+) T cells and that the expressed antigen is identical to a small fragment of myosin heavy chain. (+info)
Schistosoma mansoni activates host microvascular endothelial cells to acquire an anti-inflammatory phenotype.
(20/1591)
Since endothelial cells (ECs) play a key role in immune defense mechanisms and in immunopathology, we investigated whether the intravascular helminth parasite Schistosoma mansoni could interact with and activate resting ECs in vitro. Microscopic analysis revealed that the lung-stage schistosomula specifically attached to microvascular ECs. This adherence was associated to active cellular processes involving actin filament formation. Since variation of permeability of cultured capillary brain ECs is a good marker for endothelial activation, the transendothelial passage of a low-molecular-weight molecule (inulin) on monolayers of bovine brain capillary ECs (BBCEC) was measured in response to parasites. Schistosomula induced a dramatic decrease in transendothelial permeability, a characteristic marker for the generation of an anti-inflammatory phenotype to ECs. This paracellular barrier enhancing effect on endothelial monolayers was due to a soluble substance(s) (below 1 kDa in size) secreted from S. mansoni schistosomula and not by mechanisms associated to adherence between parasites and ECs. The reinforcement of the endothelial barrier function was accompanied by an elevation of intracellular concentration of cyclic AMP (cAMP). The use of specific kinase inhibitors confirms that schistosomula activate ECs through a cAMP/protein kinase A pathway that leads to an increased phosphorylation of the myosin light-chain kinase. These combined findings suggest that the secretory/excretory products from schistosomula possess anti-inflammatory factor(s) that signal host microvascular endothelium. The immunological consequences of such activation are discussed. (+info)
Development of antibody isotype responses to Schistosoma mansoni in an immunologically naive immigrant population: influence of infection duration, infection intensity, and host age.
(21/1591)
We have identified the influence of host and parasite factors that give rise to characteristic antibody isotype profiles with age seen in human populations living in different areas of schistosomiasis endemicity. This is important in the immunobiology of this disease. It is also of interest in the context of human responses to chronic antigen stimulation, vaccines, allergens, and other pathogens. In populations exposed to endemic schistosomiasis, factors such as intensity and duration of infection are age dependent. They therefore confound the influence of host age on antiparasite responses. Here, we resolved these confounding factors by comparing the developing antibody responses of an immunologically naive immigrant population as they acquired the infection for the first time with those of chronically infected resident inhabitants of the same region of Schistosoma mansoni endemicity in Kenya. Recent arrival in the area strongly favored immunoglobulin G3 (IgG3) responses against the parasite. The antibody isotype responses associated with human susceptibility to reinfection after chemotherapy were elevated in those suffering high intensities of infection (IgG4 responses against worm and egg antigens) or were characteristic responses of young children irrespective of the intensity or duration of infection (IgG2 responses against egg antigen). IgE responses against the adult worm, a response associated with resistance to reinfection after chemotherapy, increased with the ages of infected individuals and were also favored in those currently suffering higher intensities of infection. (+info)
Neonatal exposure to idiotype induces Schistosoma mansoni egg antigen-specific cellular and humoral immune responses.
(22/1591)
Exposure of neonatal mice to appropriate, cross-reactive Id (CRI) preparations alters immune responsiveness, ameliorates pathology, and prolongs survival of animals upon subsequent Schistosoma mansoni infection. However, because schistosome infections profoundly affect host immunobiology, which responses are effected by neonatal Id exposure alone and which responses are influenced by infection is unclear. To directly examine the schistosome soluble egg Ag (SEA)-specific immune responses altered by CRI exposure, neonatal mice were injected with CRI-expressing (CRI+) SEA-specific Ab preparations, SEA-specific Abs that did not express CRI (CRI-), or normal mouse Ig. At 9 wk of age, only mice that were neonatally exposed to CRI+ anti-SEA Abs displayed significant SEA-specific IgG serum levels and spleen cell proliferative responses. SEA-stimulated spleen cells from these CRI+-exposed mice also produced IFN-gamma, although not at significantly higher levels than mice receiving CRI- Id or normal mouse Ig. If CRI+-exposed mice were also injected with SEA at 8 wk of age, the 9-wk IFN-gamma responses were significantly higher than those of the other neonatal injection groups. The presence of both CRI and anti-CRI in the sera of animals neonatally injected with CRI, but receiving no exposure to S. mansoni Ags or infection, suggested a functional idiotypic network led to these responses. These data demonstrate that appropriate idiotypic exposure induces B and T cell responsiveness to the Ag recognized by the Id and support the hypothesis that neonatal idiotypic exposure can be an important immunoregulatory factor in schistosomiasis. (+info)
Studies with double cytokine-deficient mice reveal that highly polarized Th1- and Th2-type cytokine and antibody responses contribute equally to vaccine-induced immunity to Schistosoma mansoni.
(23/1591)
A fundamental obstacle to vaccine development in schistosomiasis mansoni is a lack of understanding of what type of an immune response should be invoked. We have addressed this central issue by using the radiation-attenuated cercariae vaccine in mice genetically engineered to exhibit highly polarized type 1 (IL-10/IL-4-deficient) or type 2 (IL-10/IL-12-deficient) cytokine and Ab phenotypes. Our data show that while significant differences in immunity exist after a single vaccination with irradiated cercariae in double cytokine-deficient vs wild-type mice, these differences disappear after two vaccinations. The most important finding of these studies, however, was revealed in vaccinated IL-10-deficient mice. These mice developed a mixed and elevated type 1- and type 2-associated immune response and developed anti-schistosome immunity at levels equal to or better than those in wild-type mice. This immunity in IL-10-deficient mice correlated with higher parasite-specific Ab titers, greater proliferative capacity of lymphocytes, increased frequency of IFN-gamma- and IL-4-secreting cells, elevated perivascular/peribronchial inflammatory responses in the lung, and greater in vitro schistosomulacidal capacity of parasite Ag-elicited cells. These results suggest that optimal vaccine-induced immunity against schistosomes is linked not to the development of a highly polarized response, but, rather, to the induction of both type 1- and type 2-associated immune responses. (+info)
Intranasal administration of a Schistosoma mansoni glutathione S-transferase-cholera toxoid conjugate vaccine evokes antiparasitic and antipathological immunity in mice.
(24/1591)
Mucosal administration of Ags linked to cholera toxin B subunit (CTB) can induce both strong mucosal secretory IgA immune responses and peripheral T cell hyporeactivity. In this study, intranasal (i.n. ) administration of CTB-conjugated Schistosoma mansoni 28-kDa GST (CTB-Sm28GST) was found to protect infected animals from schistosomiasis, especially from immunopathological complications associated with chronic inflammation. Worm burden and liver egg counts were reduced in infected animals treated with the CTB-Sm28GST conjugate as compared with mice infected only, or with mice treated with a control (CTB-OVA) conjugate. However, a more striking and consistent effect was that granuloma formations in liver and lungs of mice treated with CTB-Sm28GST were markedly suppressed. Such treatment was associated with reduced systemic delayed-type hypersensitivity and lymphocyte proliferative responses to Sm28GST. Production of IFN-gamma, IL-3, and IL-5 by liver cells was also markedly reduced after i.n. treatment of CTB-Sm28GST, whereas IL-4 production was not impaired. Intranasal treatment of infected mice with CTB-Sm28GST increased IgG1-, IgG2a-, IgA-, and IgE-Ab-forming cell responses in liver in comparison with treatment with CTB-OVA, or free Sm28GST. Most importantly, mucosal treatment with CTB-Sm28GST significantly reduced animal mortality when administered to chronically infected mice. Our results suggest that it may be possible to design a therapeutic vaccine against schistosomiasis that both limits infection and suppresses parasite-induced pathology. (+info)