Effect of Schistosoma mansoni infection on offsprings born from infected mothers

Offsprings C57BL/6 mice (4 weeks old) coming from either moderately infected (40 S. mansoni cercariae) or heavily infected (100 S. mansoni cerariae) mothers, were exposed to 40 S. mansoni cercariae each. Seven weeks post infection (P.I.), Offsprings were sacrificed. In both groups there was significant reduction in the worm load, both hepatic and intestinal tissue egg count. The oogram profile was not altered. Humoral immune response as regards the level of anti S. mansoni SEA Ab was elevated in both groups in comparison to their parallel controls at 2 weeks post delivery and 7 weeks P.I. The level of antibodies was significantly higher in heavily infected Offsprings than that present in offsprings coming from moderately infected mothers. Delayed footpad swelling and hepatic granuloma size were significantly reduced in both groups comparing with their corresponding controls.     

Features of Schistosoma mansoni infection in SCID mice

Features of Schistosoma mansoni infection in SCID mice, which lack functional T- and B-lymphocytes, were investigated. The retarded development of parasites as well as reduction of liver egg recovery in SCID mice was significantly lower than those in congenic counterpart C.B-17 mice. Furthermore, the rate of parasite recovery from SCID mice with primary infection was always lower than that from C.B-17 mice by 20%, showing the innate resistance to S. mansoni infection. SCID mice vaccinated with UV-attenuated S. mansoni cercariae did not show protective immunity against a homologous challenge infection. The present innate resistance exhibited in SCID mice is discussed in relation to cell mediated immunity of macrophage activation by IFN-gamma which would not involve T-lymphocytes but is initiated by IL-12 and TNF-alpha cytokines. SCID mice may provide novel information on the host-parasite relationship in schistosome infections.     

Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice

An important issue of concern for drug analysis in hair is the change in the drug concentration induced by the cosmetic treatment of hair. The products used for this treatment are strong bases and they are expected to cause hair damage. As a result drugs may be lost from the hair matrix or, under conditions of environmental contamination, be more easily incorporated into the hair matrix. We investigated the effects of cosmetic treatment in vivo by analysing hair samples selected from people who had treated their hair by bleaching or dyeing before sample collection. All of the subjects admitted a similar drug consumption during the time period for which the strands were analysed. Samples were viewed under a microscope to establish the degree of hair damage. Treated and untreated portions from each lock of hair were then selected, separated and analysed by standard detection procedures for cocaine, opiates, cannabinoids and nicotine. In all cases the drug content in hair that had undergone cosmetic treatment decreased in comparison to untreated hair. The majority of the mean differences were in the range of 40%-60% (cocaine, benzoylecgonine, codeine, 6-acetylmorphine and THC-COOH). For morphine the mean difference was higher than 60%, and two cases (THC and nicotine) differed by approx. 30%. These differences depended not only on the type of cosmetic treatment, as bleaching produced higher decreases than dyeing, but also on the degree of hair damage i.e. the more damaged the hair, the larger the differences in the concentration levels of drugs.     

Isotype responses to candidate vaccine antigens in protective sera obtained from mice vaccinated with irradiated cercariae of Schistosoma mansoni

In experimental schistosomiasis, sera of mice multiply vaccinated with radiation-attenuated cercariae of Schistosoma mansoni passively transfer resistance against cercarial challenge to naive mice. To further characterize these sera, we tested their protective capacities in two mouse strains (C57BL/6J and CBA/J) and compared the antigen-specific isotype compositions of the different protective sera by means of the enzyme-linked immunosorbent assay. By using an array of purified schistosomal antigens, the patterns of antibody titers and isotypes differed for each experimental group and antigen. In the most-protective C57BL/6J sera, high levels of immunoglobulin G1 (IgG1), IgG2a, and IgG2b bound to heat shock protein 70 and the integral membrane protein Sm23, whereas recognition of these antigens by less-protective CBA/J sera was lower. Glutathione S-transferase (GST) was recognized predominantly by IgM antibodies of all vaccinated groups, and a significant portion of this response was directed against carbohydrate epitopes. Antibodies specific for triosephosphate isomerase, paramyosin, and Sm32 (hemoglobinase) were present in less-protective sera and thus seem less relevant for passive transfer of resistance. The results of this study suggest a contribution of IgG antibodies specific for heat shock protein 70 and Sm23, and possibly a contribution of GST-specific IgM antibodies, to the protective effect of sera from C57BL/6J mice vaccinated with irradiated cercariae.     

Pairing of Schistosoma mansoni males in infected Syrian hamsters

Pairing of male schistosomes in the liver of infected hamsters was recorded with Egyptians S. mansoni strain. The homospecific male pairs never carried each other in the gynaecophoric duct, but they being closed in either central or hepatic veins. Other perfused males and females en copula showed normal mating behaviour. The paired males were more or less in the same size. The random sexed miracidia used resulted in obtaining 1:2.1 female/male ratio. It is concluded that the random increase of male schistosomes may create the male pairing behaviour. Also, the migration of female against the blood stream to the mesenteric plexus of the host and the failure of male to catch them may lead to this homosexual pairing. The black haemozoin-like substance seen in mature females was also observed in the pairing males and this probably reflects the effect of scarcity or migration of females to the mesenteric plexus.     

Studies on experimental mixed infection of Schistosoma haematobium and Schistosoma mansoni

Swiss Albino mice have been infected with S. haematobium and challenged 4 weeks later with S. mansoni. Parasitological, pathological and ultrastructural studies were done. The results revealed cross mating between the two species. A reduction in S. mansoni worm load, egg count, hepatic granuloma number and size was noticed. The presence of heterologous immunity was suggested.     

Involvement of regional lymph nodes after penetration of Schistosoma mansoni cercariae in naive and infected mice

The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A beta complexes in the brain. Further characterizations of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD.     

Protection against tuberculosis by passive transfer with T-cell clones recognizing mycobacterial heat-shock protein 65

We have previously shown that mice vaccinated by injection with J774 macrophage-like tumour cells that expressed Mycobacterium leprae heat-shock protein (hsp) 65 as a transgene had acquired a remarkably high degree of protection against subsequent challenge with virulent M. tuberculosis. We show here that antigen-specific T cells cloned from spleens of such vaccinated animals can transfer a high level of protection to non-vaccinated recipients. The most efficient cells were of T-cell receptor (TCR) alpha beta+ and CD4- CD8+ type and specifically lysed mycobacteria-infected macrophages. These findings are consistent with the importance for protective immunity of engaging the endogenous antigen-presenting pathway to bias the immune response towards a cytolytic action against a mycobacterial antigen that is expressed at the surface of infected macrophages. TCR gamma delta+ and TCR alpha beta+ cells interacted synergistically.     

Immunological response of major histocompatibility complex class II-deficient (Abeta(o)) mice infected by the parasite Schistosoma mansoni

This study investigated changes in autonomic nervous activities due to psychological stress in Type A females. Eight Type A and eight Type B females performed a psychomotor task for 30 minutes. Power spectral analysis of heart rate variability (HRV) was used to examine the autonomic nervous activities. Results showed the low frequency (LF) component and LF/HF ratio in Type A females increased after the onset of the task. There were no significant differences in task performance between Type A and Type B females. The subjective mental workload increased gradually in Type A females during the tasks, whereas in Type B females this parameter did not change in a consistent manner. The results suggest that the sympathetic nervous system in Type A females was more stimulated by the task and Type A females felt a greater subjective mental workload than did Type B females.     

Tegument changes of Schistosoma japonicum and Schistosoma mansoni in mice treated with artemether

AIM: To study the effect of artemether (Art) on the tegument of schistosomes. METHODS: Mice infected with S japonicum cercariae for 7 and 35 d, or with S mansoni cercariae for 49 d were treated intragastrically with Art 200-300 mg.kg-1.d-1 for 2 d. Schistosomes were collected in groups of 2 mice at various intervals after medication for scanning electron microscopic observation. RESULTS: The tegumental changes induced by Art appeared to be similar in S japonicum and S mansoni: swelling and fusion of tegumental surfaces, vesicle formation and collapse of discoid-like sensory structures. In S japonicum the emergence of tegumental alterations was earlier in 7-d-old schistosomulae than that in 35-d-old adult worms. CONCLUSION: Art injured the teguments of S japonicum and S mansoni.     

Comparative effect of tiaprofenic acid and piroxicam alone and as adjuvants to praziquantel in Schistosoma mansoni infected mice

A simple, rapid and sensitive two column-switching high-performance liquid chromatographic (HPLC) method with ultraviolet detection at 210 nm has been developed for the determination of N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (AY4166, I) and its seven metabolites in human plasma and urine. Measurements of I and its metabolites were carried out by two column-switching HPLC, because metabolites were classified into two groups according to their retention times. After purification of plasma samples using solid-phase extraction and direct dilution of urinary samples, I and each metabolite were injected into HPLC. The calibration graphs for plasma and urinary samples were linear in the ranges 0.1 to 10 microg ml(-1) and 0.5 to 50 microg ml(-1), respectively. Recoveries of I and its seven metabolites were over 88% by the standard addition method and the relative standard deviations of I and its metabolites were 1-6%.     

A trial to enhance the efficiency of Cyclosporin A in the treatment of Schistosoma mansoni infection by immunization of mice

Cyclosporin A (CsA) acts in two distinct modes against Schistosoma mansoni (S. mansoni) infection. It behaves in part as an antihelminthic and also as an immunomodulator. In this study, two methods were performed to increase the efficacy of the subcurative dose of CsA (30 mg/kg). These methods were, passive immunization where the drug was given simultaneously with rabbit antisera post infection and active immunization where the worm surface antigen was given prior to infection. The results showed that both methods led to enhancement of the curative effect of the CsA. However, the active immunization gave more significant reduction in liver worm and egg loads. Histopathological study showed small size and few number of hepatic granulomas in the passively immunized group while in the active group, there was just few and small collection of inflammatory cells. Moreover, the indirect fluorescent antibody test visualized damage to the worm tegument in both types of immunization. Thus, it could be concluded that active immunization increased the immunomodulatory effect of CsA in treatment of S. mansoni with less toxic effects by using a subcurative dose.     

Fc epsilonRI-deficient mice infected with Schistosoma mansoni mount normal Th2-type responses while displaying enhanced liver pathology

The IgE/Fc epsilonRI interaction is postulated to play an important role in resistance to helminths both at the level of anti-parasitic effector cell function and in the initiation of Th2 responses through IL-4 produced by Fc epsilonRI+ non-B, non-T (NBNT) cells. To formally evaluate the role of IgE/Fc epsilonRI signaling in the host response to helminths we studied Schistosoma mansoni infection in Fc epsilonRI knockout (KO) mice. Infected wild-type (wt) and KO animals showed comparable adult worm and tissue egg burdens, arguing against a role for Fc epsilonRI interactions in host resistance. Significantly, NBNT cells from infected KO, in contrast to wt animals, did not secrete IL-4 when stimulated with anti-IgE Ab or soluble parasite Ag. Nevertheless, serum IgE levels and Th2 cytokine production profiles were comparable in both strains of mice, demonstrating that the Ag-dependent stimulation of IL-4 secretion by NBNT cells is not essential for helminth-induced Th2 differentiation. However, when stimulated with low Ag doses, splenocytes from infected Fc epsilonRI-deficient mice produced less IL-4 in vitro than similar cultures from infected wt animals, an effect attributable to their defective NBNT cell function. Moreover, infected KO mice showed enhanced egg granuloma formation and hepatic fibrosis, revealing that the IgE/Fc epsilonRI interaction, while not essential for Th2 response development or resistance to primary infection, plays a significant role in down-regulating host pathology.     

Protection of mice against lethal coxsackievirus B3 infection by using DNA immunization

Vaccination with DNA and recombinant vaccinia viruses (rec.VV) has been studied with the coxsackievirus B3 (CVB3) model system. Plasmids encoding all structural proteins of CVB3, when injected intramuscularly, induced only low levels of virus-specific antibodies. However, DNA vaccination with the major structural protein VP1 protected 72.2% of mice from lethal challenge, whereas VP1 expressed by rec.VV was much less efficient.     

Modification of the lung recovery assay for schistosomula and correlations with worm burdens in mice infected with Schistosoma mansoni

The kinetics of recovery of schistosomula from the lungs of previously-unexposed CF1 mice were studied following infection with Schistosoma mansoni cercariae. Lung tissue fragments were incubated from 3 to 48 hr and the completeness of recovery of viable schistosomula was determined. The recovery of schistosomula from the lungs was shown to correlate closely with 7-week worm recoveries. With the additional incubation described, the lung recovery assay may provide a more defined indicator of protective immunity. Based on the data generated by these analyses, it is predicted that under these conditions schistosomula arrive in the lungs from 3 to 7 days after infection, and that they sojourn there for a 3-day period.     

Synthesis and characterization of a protective peptide-based vaccine against Schistosoma mansoni

Two synthetic peptides, corresponding to the N-terminal sequence of the 45-kDa subunit of the protective 9B antigen of Schistosoma mansoni and differing in only one amino acid residue, were synthesized. These peptides were recognized by the protective monoclonal antibody 152-66-9B, as well as by sera of mice and humans infected with schistosomiasis. The peptides were coupled to a protein carrier and used for immunization. One of the peptides, 9B-peptide1, induced in mice significant protection against challenge infection, manifested in a 40 to 50% reduction in worm burden.     

Fc epsilon receptor-positive cells are a major source of antigen-induced interleukin-4 in spleens of mice infected with Schistosoma mansoni

When cultured in vitro with either mitogen or parasite antigens, spleen cells from mice infected with Schistosoma mansoni produce significantly higher levels of IL-4 than splenocytes from control animals. Previous studies suggested that this increase in IL-4 production occurs because of a selective expansion of T helper type 2 (Th2) cells in infected mice. However, these experiments employed unfractionated spleen populations rather than purified T lymphocytes. Here we demonstrate that T-depleted spleen cells from infected animals synthesize high levels of interleukin-4 (IL-4), but no IL-5 when stimulated with parasite antigen in vitro. Nevertheless, when purified by sorting, T cells and non-B, non-T (NBNT) populations produced similar amounts of IL-4 in response to parasite antigen. The IL-4 producing NBNT cells were found to belong to an Fc epsilon receptor (Fc epsilon R)-positive population which after sort purification produced high levels of IL-4 (between 1000 and 2000 U of per 5 x 10(3) cells). FACS analysis revealed that these Fc epsilon R+ cells make up 0.53% of splenic NBNT cells in control animals while in 8-9-week-infected animals they increase to 3.8% of that population. In contrast, in mice with 8-week unisexual worm infections these cells comprise only 1.71% of NBNT cells, indicating that eggs are a major stimulus of the response. The expansion of Fc epsilon R+ cells and their production of IL-4 could be an important factor regulating the selection and induction of different CD4+ subsets in schistosome-infected hosts.