Protective human IgE responses are promoted by comparable life-cycle dependent Tegument Allergen-Like expression in Schistosoma haematobium and Schistosoma mansoni infection.

Schistosoma haematobium is the most prevalent of the human-infecting schistosome species, causing significant morbidity in endemically exposed populations. Despite this, it has been relatively understudied compared to its fellow species, S. mansoni.

Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity.

Allergic reactions can be considered as maladaptive IgE immune responses towards environmental antigens. Intriguingly, these mechanisms are observed to be very similar to those implicated in the acquisition of an important degree of immunity against metazoan parasites (helminths and arthropods) in mammalian hosts. Based on the hypothesis that IgE-mediated immune responses evolved in mammals to provide extra protection against metazoan parasites rather than to cause allergy, we predict that the environmental allergens will share key properties with the metazoan parasite antigens that are specifically targeted by IgE in infected human populations.

Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.

Background: The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study).

Known Allergen Structures Predict Schistosoma mansoni IgE-Binding Antigens in Human Infection.

The IgE response has been associated with both allergic reactions and immunity to metazoan parasites. Recently, we hypothesized that all environmental allergens bear structural homology to IgE-binding antigens from metazoan parasites and that this homology defines the relatively small number of protein families containing allergenic targets. In this study, known allergen structures (Pfam domains) from major environmental allergen families were used to predict allergen-like (SmProfilin, SmVAL-6, SmLipocalin, SmHSP20, Sm triosephosphate isomerase, SmThioredoxin, Sm superoxide dismutase, SmCyclophilin, and Sm phosphoglycerate kinase) and non-allergen-like [Sm dynein light chain (SmDLC), SmAldolase SmAK, SmUbiquitin, and Sm14-3-3] proteins in Schistosoma mansoni.

Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties.

The tegumental allergen-like (TAL) proteins from Schistosoma mansoni are part of a family of calcium binding proteins found only in parasitic flatworms. These proteins have attracted interest as potential drug or vaccine targets, yet comparatively little is known about their biochemistry. Here, we compared the biochemical properties of three members of this family: SmTAL1 (Sm22.

Use of humanised rat basophilic leukaemia cell line RS-ATL8 for the assessment of allergenicity of Schistosoma mansoni proteins.

Background: Parasite-specific IgE is thought to correlate with protection against Schistosoma mansoni infection or re-infection. Only a few molecular targets of the IgE response in S. mansoni infection have been characterised.

Maternal hookworm modifies risk factors for childhood eczema: results from a birth cohort in Uganda.

Background: Worms may protect against allergy. Early-life worm exposure may be critical, but this has not been fully investigated.

Objectives: To investigate whether worms in pregnancy and in early childhood are associated with childhood eczema incidence.

Human Schistosoma haematobium antifecundity immunity is dependent on transmission intensity and associated with immunoglobulin G1 to worm-derived antigens.

Background: Immunity that reduces worm fecundity and, in turn, reduces morbidity is proposed for Schistosoma haematobium, a parasite of major public health importance. Mathematical models of epidemiological trends suggest that antifecundity immunity is dependent on antibody responses to adult-worm-derived antigen.

Methods: For a Malian cohort (age, 5-29 years) residing in high-transmission fishing villages or a moderate-transmission village, worm fecundity was assessed using the ratio of urinary egg excretion to levels of circulating anodic antigen, a Schistosoma-specific antigen that is steadily secreted by adult worms.

Suppression of basophil histamine release and other IgE-dependent responses in childhood Schistosoma mansoni/hookworm coinfection.

Background: The poor correlation between allergen-specific immunoglobulin E (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm.

Methods: Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment.

Human IgE responses to different splice variants of Schistosoma mansoni tropomyosin: associations with immunity.

Resistance to Schistosoma mansoni infection has been correlated with IgE responses to the adult worm. Molecular targets of this response are gaining interest as markers of immunity and as indicators of allergenic properties. Few protein families contain IgE antigens (allergens) and one of the most highly represented are the tropomyosins.

Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity.

The Th2 immune response, culminating in eosinophilia and IgE production, is not only characteristic of allergy but also of infection by parasitic worms (helminths). Anti-parasite IgE has been associated with immunity against a range of helminth infections and many believe that IgE and its receptors evolved to help counter metazoan parasites. Allergens (IgE-antigens) are present in only a small minority of protein families and known IgE targets in helminths belong to these same families (e.

Effects of treatment on IgE responses against parasite allergen-like proteins and immunity to reinfection in childhood schistosome and hookworm coinfections.

Naturally occurring human immunity to both schistosomiasis and hookworm infection has been associated with IgE responses against parasite allergen-like proteins. Since the two helminths frequently coinfect the same individuals, there is growing advocacy for their concurrent treatment. However, both helminths are known to exert strong immunomodulatory effects; therefore, coinfected individuals could have immune responses different from those characteristically seen in monoinfected individuals.

Progressive cross-reactivity in IgE responses: an explanation for the slow development of human immunity to schistosomiasis?

People in regions of Schistosoma mansoni endemicity slowly acquire immunity, but why this takes years to develop is still not clear. It has been associated with increases in parasite-specific IgE, induced, some investigators propose, to antigens exposed during the death of adult worms. These antigens include members of the tegumental-allergen-like protein family (TAL1 to TAL13).

The Schistosoma mansoni tegumental-allergen-like (TAL) protein family: influence of developmental expression on human IgE responses.

Background: A human IgE response to Sm22.6 (a dominant IgE target in Schistosoma mansoni) is associated with the development of partial immunity. Located inside the tegument, the molecule belongs to a family of proteins from parasitic platyhelminths, the Tegument-Allergen-Like proteins (TALs).

Anthelminthic treatment during pregnancy is associated with increased risk of infantile eczema: randomised-controlled trial results.

Background: Allergy is commoner in developed than in developing countries. Chronic worm infections show inverse associations with allergy, and prenatal exposures may be critical to allergy risk.

Objective: To determine whether anthelminthic treatment during pregnancy increases the risk of allergy in infancy.

Influence of exposure history on the immunology and development of resistance to human Schistosomiasis mansoni.

Background: Previous studies suggest that humans can acquire immunity to reinfection with schistosomes, most probably due to immunologic mechanisms acquired after exposure to dying schistosome worms.

Methodology/principal Findings: We followed longitudinally two cohorts of adult males occupationally exposed to Schistosoma mansoni by washing cars (120 men) or harvesting sand (53 men) in Lake Victoria. Men were treated with praziquantel each time S.

Survival of the fittest: allergology or parasitology?

Allergologists have long recognized that only a small fraction of the environmental and food proteins that we are exposed to give rise to IgE responses. This has raised the intriguing and important question: What makes an allergen an allergen? Many protein allergens have close homologs in metazoan parasites, and as helminth genome information grows, it appears increasingly clear that not only are the immune mechanisms of allergy and anti-helminth immunity closely related, but so are the helminth and allergen proteins that induce them. This suggests that at least part of the secret of what allows some proteins to be allergens may actually lie in the long co-evolutionary relationship between worms and their vertebrate (and latterly human) hosts.

Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses.

Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. mansoni egg antigen [SEA]) induce strong Th2 responses both in vitro and in vivo. However, the specific molecules that prime the development of Th2 responses have not been identified.

Factors affecting human IgE and IgG responses to allergen-like Schistosoma mansoni antigens: Molecular structure and patterns of in vivo exposure.

Background: The human IgE response is associated with allergy and with host defence against parasitic worms. A response to Sm22.6, the dominant IgE antigen in adult Schistosoma mansoni worms, correlates with resistance to re-infection after treatment.

Eosinophil activity in Schistosoma mansoni infections in vivo and in vitro in relation to plasma cytokine profile pre- and posttreatment with praziquantel.

Eosinophil activity in vivo and in vitro was studied in relation to infection intensities and plasma cytokine profiles of 51 Schistosoma mansoni-infected Ugandan fishermen before treatment and 24 h and 3 weeks posttreatment. Blood eosinophil numbers significantly declined 24 h posttreatment, but significant eosinophilia had developed by 3 weeks posttreatment. Cellular eosinophil cationic protein (ECP) content increased significantly during the transient eosinopenia but was significantly reduced 3 weeks later.

Applied and basic research on the epidemiology, morbidity, and immunology of schistosomiasis in fishing communities on Lake Albert, Uganda.

We report multidisciplinary studies on schistosomiasis which have been ongoing in the fishing communities of Piida, Booma, Bugoigo and Walakuba, on Lake Albert, Uganda, since 1996. Schistosomiasis is the major health problem in this area, with high infection intensities and prevalence. In addition to generating basic data on the epidemiology, morbidity and immunology of human schistosomiasis, this research programme is providing important descriptive and methodological information, and has contributed to the increase in operational capacity within Uganda in recent years.

Chemotherapy for schistosomiasis in Ugandan fishermen: treatment can cause a rapid increase in interleukin-5 levels in plasma but decreased levels of eosinophilia and worm-specific immunoglobulin E.

Chemotherapy for blood-dwelling schistosomes kills the worms and exposes parasite antigen to the circulation. In many people from areas of endemicity, this treatment increases parasite-specific immunoglobulin E (IgE) and other Th2 responses in the months following therapy, responses that have been associated with subsequent resistance to reinfection. Here we investigate much earlier changes in immune reactions after praziquantel therapy in Schistosoma mansoni-infected fishermen working in an area of high transmission in Uganda.

Changes in IgE- and antigen-dependent histamine-release in peripheral blood of Schistosoma mansoni-infected Ugandan fishermen after treatment with praziquantel.

Background: Parasite-specific IgE levels correlate with human resistance to reinfection with Schistosoma spp. after chemotherapy. Although the role of eosinophils in schistosomiasis has been the focus of a great deal of important research, the involvement of other Fcepsilon receptor-bearing cells, such as mast cells and basophils, has not been investigated in relation to human immunity to schistosomes.