Experimental Schistosoma Mansoni Infection Research Articles

Potential i-Nos/Arg-1 Switch with NLRP3 and Parasitic Load Down Regulation in Experimental Schistosoma mansoni Infection via Chloroquine Repurposing.

In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double-bladed sword in schistosomiasis (anti-inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i-Nos/Arg-1 expression, splenomegaly, hepatic insult and NLRP3-immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel-induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i-Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i-Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage-1 polarisation. On the flip side, the chloroquine-induced low Arg-1 seemed to abate immune tolerance and probably macrophage-2 polarisation. Collectively, chloroquine synergised the praziquantel-schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis.

Effect of celecoxib against different developmental stages of experimental Schistosoma mansoni infection

Due to the high prevalence of schistosomiasis and the wide use of praziquantel solely for mass drug administration to control the disease, there is a great concern about the potential emergence of reduced susceptibility strains. This, together with the concern that praziquantel is ineffective against juvenile worms highlight the importance of developing an alternative anti-schistosomal drug. Using nonsteroidal anti-inflammatory drugs against schistosome infection is considerable. The present study evaluated the effect of oral administration of five days celecoxib regimen (20 mg/kg/day) against different developmental stages of Schistosoma mansoni infection. This regimen induced significant reduction in worm burden, tissue egg count, individual female fecundity and the mean percentage of immature and mature eggs with increased mean percentage of dead eggs. More importantly, celecoxib was more potent than praziquantel in all these parasitological parameters (except in the worm burden when given against the adult stage where the difference was statistically non-significant). Scanning and transmission electron microscopy of the adult worms revealed severe tegumental damage, laceration of the muscular layers and oedema of the syncytial layer. There was disruption of the testicular, ovarian and vitelline glandular tissues with signs of apoptosis and abnormalities of the spermatozoa and the oocytes. Additionally, celecoxib induced reduction in the number and the size of the hepatic granulomata and also amelioration of the hepatic tissue pathology.

The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice

Schistosoma mansoni is less susceptible to the antiparasitic drug ivermectin than other helminths. By inhibiting the P-glycoprotein or cytochrome P450 3A in mice host or parasites in a murine model, we aimed at increasing the sensitivity of S. mansoni to the drug and thus preventing infection. We assigned 124 BALB/c mice to no treatment, treatment with ivermectin only or a combination of ivermectin with either cobicistat or elacridar once daily for three days before infecting them with 150 S. mansoni cercariae each. The assignment was done by batches without an explicit randomization code. Toxicity was monitored. At eight weeks post-infection, mice were euthanized. We determined number of eggs in intestine and liver, adult worms in portal and mesenteric veins. Disease was assessed by counting granulomas/cm2 of liver and studying organ weight indices and total weight. IgG levels in serum were also considered. No difference between groups treated with ivermectin only or in combination with cobicistat or elacridar compared with untreated, infected controls. Most mice treated with ivermectin and elacridar suffered severe neurological toxicity. In conclusion, systemic treatment with ivermectin, even in the presence of pharmacological inhibition of P-glycoprotein or cytochrome P450 3A, did not result in effective prophylaxis for S. mansoni infection in an experimental murine model.

Imbalance of Steroid Hormones in Hamsters Infected with Schistosoma mansoni.

Schistosomiasis is a debilitating disease that affects 200 million people worldwide. Schistosoma haematobium and Schistosoma mansoni are the major causative agents of this disease. Cancer-association and infertility-association in Schistosoma haematobium infection have already been described and it is known that the parasite produces a catechol-estrogen molecule that induces a hormonal imbalance in the host. In order to better understand the relation of hormonal imbalance in experimental Schistosoma mansoni infection, we investigated a serum panel of steroid hormones in Schistosoma mansoni infected hamsters. We found a decrease in the serum levels of Estradiol (E2), Testosterone and Progesterone in infected females and an increase of Testosterone and a decrease in Progesterone in infected males in comparison with controls. These results indicate that S. mansoni alters the levels of steroid hormones in infected males and females and it will increase the repertoire of data about the host-parasite molecular interplay and its relation with the endocrine system.

Assessment of the potential therapeutic effects of omeprazole in Schistosoma mansoni infected mice.

Schistosomiasis is a neglected chronic parasitic disease with a significant lasting morbidity. Currently, praziquantel (PZQ) is the most efficient drug for schistosomiasis worldwide. However, the possibility of the occurrence of resistance to PZQ is increasing. Therefore, there is a vital need to find new antischistosomal drugs or to increase the efficacy of the existing ones. Omeprazole is a proton pump inhibitor which is reported to have antiparasitic properties. Thus, the aim of this study was to assess the potential therapeutic effects of omeprazole in experimental Schistosoma mansoni infection either alone or in combination with PZQ. For this aim, 80 laboratory bred mice were divided into 3 groups; uninfected control, infected untreated control, and infected and treated at tenth week P.I. The last group was divided into three subgroups that received either PZQ alone, omeprazole alone, or both drugs. The effectiveness of treatment was assessed by adult worm counts, liver egg count, scanning electron microscopy of adult worms, histopathological, and immunohistochemical (GFAP) examination. There was significant reduction of adult worm counts, liver egg counts, size, diameter of hepatic granulomas, hepatic fibrosis, and GFAP expression in the group that received combined treatment as compared to PZQ group. Moreover, the tegumental changes were more evident in the group that received combined treatment. In conclusion, the administration of omeprazole with PZQ improved the efficacy of PZQ in the treatment of Schistosomiasis mansoni.

Effect of omega-3 fatty acids administered as monotherapy or combined with artemether on experimental Schistosoma mansoni infection

Schistosomiasis is on the top list of endemic diseases in sub-Saharan Africa. Praziquantel is the drug of choice for treatment of human schistosomiasis. Yet, the sole dependence on the drug raises concerns about the potential for increased drug resistance, which would subsequently result in searching for alternative preventive chemotherapy options, ideally among natural compounds. Therefore, we conducted this work to assess the effect of omega-3 polyunsaturated fatty acids [(ω-3) PUFAs] monotherapy or combined therapy with artemether (ART) against Schistosoma mansoni infection in a mouse model. A total of 42 mice were divided into 4 groups and infected with 50 ± 5 S. mansoni cercariae for 10 weeks. Mice were treated orally with either (ω-3) PUFAs as 273 mg/ kg, 4 times/ week throughout the experiment, ART as a single dose of 400 mg/ kg, 3 weeks post-infection, or combined ART + (ω-3) PUFAs using the same respective treatment regimen, while infected untreated mice were served as controls. The study explored that combined administration of (ω-3) PUFAs and ART has the best schistosomicidal efficacy as it significantly reduced liver and spleen indices, worm count, egg burdens, and granulomas count as well as diameter. Besides, the combined regimen was associated with a significant decrease in both hepatic nitric oxide and serum interleukin-4 level. The results highlighted the possibility of using (ω-3) PUFA combined with ART as a novel anti-schistosomal combination therapy. However, further researches should be conducted to clarify the possible synergistic mechanism/s between the two natural compounds.

Complementary effect of Capparis spinosa L. and silymarin with/without praziquantel on mice experimentally infected with Schistosoma mansoni

SummarySchistosomiasis remains to be the most common fibrotic disease resulting from inflammation and deposition of scar tissue around trapped parasitic eggs in the liver. Though chemotherapy eradicates matured worms efficiently and prevents the accumulation of schistosome eggs, fewer effective drugs are directed to reverse the present hepatic fibrosis. Therefore, treatment targeting hepatic fibrosis associated with schistosomiasis remains a challenging proposition.The present study was designed to investigate the potential complementary schistosomicidal and hepatoprotective activities of the methanol extract of Capparis spinosa L. (C. spinosa) with or without praziquantel (PZQ) and compare results with silymarin (Milk thistle), a known hepatoprotective and antifibrotic agent, on induced liver fibrosis by experimental Schistosoma mansoni (S. mansoni) infection. Total polyphenols in the extract were determined using colorimetric assay.C. spinosa L. caused a partial decrease in worm burden; a statistically significant reduction in hepatic and intestinal tissue egg load, what was associated histopathologically with decreasing in both the number and diameter of granulomas, as well as restoring serum aminotransferases (AST & ALT), alkaline phosphatase (ALP) and improving liver albumin synthesis. The best results were obtained in the group of mice treated with C. spinosa L. and PZQ together. Quantitative estimation of total polyphenols content using colorimetric assay showed that C. spinosa L. leaves contain higher concentration of polyphenolic compounds than fruits.It was concluded that C. spinosa L. has a promising hepatoprotective and antifibrotic properties and could be introduced as a safe and effective therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis. Nevertheless further studies on the mechanism of action of C. spinosa L. in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.

Impact of treatment with a Protein Tyrosine Kinase Inhibitor (Genistein) on acute and chronic experimental Schistosoma mansoni infection

Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease.Recently, protein tyrosine kinase (PTK) inhibitors have been identified as potent anti-schistosomal and anti-fibrotic drugs against schistosomes, that may suppress and reverse Schistosoma mansoni (S. mansoni) induced liver fibrosis.The present study was designed to assess the anti-schistosomal and antifibrotic activity of Genistein, a PTK inhibitor, in comparison to PZQ, on both acute and chronic S. mansoni-infected mice using different parasitological, histopathological and immunohistochemical studies.Genistein showed a significant reduction (P < .05) in total worm burden, tissue egg load, mean hepatic granulomas diameter and numbers, percentage of collagen and expression of transforming growth factor-beta 1 (TGF-β 1) in the examined hepatocytes with elevation in percentage of degenerated ova, in comparison to the control groups, in both acute and chronic stages of infection. The best results were obtained when Genistein was combined with PZQ.Therefore, it was concluded that Genistein showed a promising anti-schistosomal and anti-fibrotic properties which could make it one of the new potential targets in chemotherapy against schistosomiasis.

Assessment of Echinacea purpurea and mefloquine in treatment of Schistosoma mansoni

Objective To assess the effect of combined Echinacea purpurea (EP) and mefloquine (MQ) in the treatment of experimental Schistosoma mansoni infection. Background Schistosomiasis is a prevalent parasitic disease in tropical and subtropical areas caused by the flatworm S. mansoni. Several medications are used in the treatment of schistosomiasis. Praziquantel (PZQ) is the drug of choice because of its safety and broad-spectrum activity. Materials and methods The current study was carried out on 120 laboratory-bred Swiss albino female mice. They were classified into six groups: group I (control), group II (PZQ treated), group III (MQ treated), group IV (EP treated), group V (PZQ and EP), and group VI (MQ and EP). Evaluation was done parasitologically using the worm count technique, ova count technique in intestine and liver, and oogram pattern and histopathological examination of liver sections for assessment of granuloma size and diameter. Moreover, electron microscopic changes of the adult worms were evaluated. Results The highest worm burden reduction of male (79.41%), female (82.28%), couples (86.6%), and total (92%) worms was obtained in the combined MQ and EP treated group. The highest reduction in the mean number of ova count/g tissue in either the intestine (93%) or the liver (89%) was detected in MQ and EP treated group. In combined treated groups, the highest percentage of reduction in the immature and mature eggs was detected in the group MQ and EP; it was 9.16 ± 4.11 and 5.25 ± 2.56, respectively. Moreover, there was an increase in the percentage of dead eggs (85.58 ± 6.43). The highest reductions in hepatic granuloma diameter and number were seen in the combination of MQ and EP at 67 and 85%, respectively (P Conclusion MQ has effective schistosomicidal properties through reduction of worm burden and tissue egg load. Moreover, EP extract showed promising antischistosomal activity on S. mansoni-infected mice. It is recommended to study the exact mechanism of action of EP on S. mansoni and its possible effects on other parasitic infections.

Parasitological and histopathological effects of some antischistosome drugs in Schistosoma mansoni- infected mice

Objective To assess the in-vivo effects of artemisinin (ART), arachidonic acid (ARA), and nifedipine (NIF) compared with praziquantel (PZQ) on experimental Schistosoma mansoni infection in terms of worm burden, liver histopathological, immunohistochemical alterations, cytokines changes, and scanning electron microscopy (SEM) on both juvenile and adult stages of S. mansoni in experimentally infected mice. Background Reliance on a single drug for schistosomiasis control may promote the spread of drug-resistant parasites. Materials and methods The study was carried out in Theodor Bilharz Research Institute (Giza, Egypt) in April 2015 and included 120 laboratory-bred female albino mice. These mice were divided into nine groups: group 1) uninfected and untreated), group 2 (infected untreated), group 3 (infected and ART treated), group 4 (infected and ARA treated), group 5 (infected and NIF treated), group 6 (infected and PZQ treated), group 7 (infected and ART plus PZQ treated), group 8 (infected and ARA plus PZQ treated), and group 9 (infected and NIF plus PZQ treated). Mice were subjected to worm burden, liver histopathology, and SEM. Results ART plus PZQ-treated mice showed the lowest total worm burden (6.10 ± 5.30), the lowest schistosomula stage worm burden (11.0 ± 1.58), the lowest adult stage worm burden (1.20 ± 0.83), the lowest granuloma number (1.60 ± 0.54), and the smallest granuloma diameter (100.20 ± 8.25 μm). NIF plus PZQ were the most effective on the schistosomula and the adult stages of S. mansoni; however, PZQ was the least effective on the schistosomula and ART was the least effective on the adult of S. mansoni by SEM. Conclusion A combination of ART plus PZQ was the most effective in reducing total, schistosomula stage, and adult stage worm burdens, and also the number and diameter of granuloma. NIF plus PZQ were the most effective against the schistosomula and the adult stages of S. mansoni by SEM, but PZQ was the least effective against schistosomula stage worm burden reduction and was the least effective against it by SEM.

Combination of the two schistosomal antigens Sm14 and Sm29 elicits significant protection against experimental Schistosoma mansoni infection

Schistosomiasis continues to be a serious helminthic disease that is widespread in many regions in the world. Disease management relies mainly on early treatment with praziquantel, nevertheless, re-infection rates can still be high. An effective vaccine against Schistosoma mansoni is still lacking; a situation which hinders the efforts to eradicate the disease worldwide. Most investigators test S. mansoni antigens individually, rather than in combination, in their vaccine trials. A single-antigen vaccine is likely to elicit less protection against schistosomiasis than a multi-antigen vaccine. In the current study, we have selected two promising S. mansoni antigens, Sm14 and Sm29, and investigated their combination as a potential vaccine. Recombinant Sm14 and a truncated form of Sm29, designated TrSm29, were successfully expressed in Escherichiacoli. The two antigens were purified using affinity chromatography and administered to Swiss albino mice individually and in combination. Significant protection against S. mansoni infection was observed in mice immunized with the Sm14/TrSm29 combination in the presence/absence of the immunoadjuvant poly (I:C). The poly (I:C)-adjuvanted combination resulted in 40.3%, 68.2%, and 57.9% reduction in adult worm burden, liver egg burden and intestinal eggs, respectively. Granuloma size and count were also reduced besides improvement of the histopathological picture of livers of immunized mice. This study demonstrates the importance of using multi-antigen vaccines as an effective and simple approach to fulfill enhanced protection against schistosomiasis.

Effect of a novel benzimidazole derivative in experimental Schistosoma mansoni infection

Currently, praziquantel is the only drug of choice for treatment of schistosomiasis. Reports of praziquantel resistance raise concerns about future control of the disease. Therefore, the search for new schistosomicidal drugs is eminent. In this study, the effect of a novel benzimidazole-derived compound (compound BTP-Iso) was assessed in mice harboring adult Schistosoma mansoni (Egyptian strain). Mice were treated 42days p.i. with compound BTP-Iso using two treatment regimens (200 or 300mg/kg). In both regimens, there were significant reductions in the number of recovered S. mansoni worms especially females and in immature ova, in addition to a significant reduction in the number and size of hepatic granulomata. A dose of 300mg/kg resulted in a significant decrease in intestinal and hepatic tissue egg loads. Effect on schistosomes was confirmed by scanning electron microscopy, where adult worms recovered from mice treated with 200mg/kg of compound BTP-Iso revealed tegumental alternations, characterised by swelling of tegumental ridges, bleb formation, and mild erosion in male worms; however in females, there were extensive erosion and destruction of the tegumental surface. These promising results may encourage future use of compound BTP-Iso in the treatment of schistosomiasis. However, more research is needed to detect the effect of compound BTP-Iso on early developmental stages of S. mansoni and on other species of human schistosomes.

Effect of Simultaneous and/or Consecutive Administration of the Broad Spectrum Anthelmintic Flubendazole together with Praziquantel in Experimental Schistosoma mansoni Infection

This study is a trial to demonstrate the effect of the broad spectrum anthelmintic drug flubendazole (methyl 5-(p-fluoro-benzoyl)-2-benzimidazolecarbamate, CAS 31430-15-6), a mebendazole derivative, together with praziquantel (CAS 55268-74-1, EMBAY 8440, Biltricide) in murine schistosomiasis mansoni. Moreover, the relationship between the posttreatment worm burden, oogram pattern, tissue egg load and hepatic granuloma volume was also investigated. Three main groups of Swiss albino mice infected with Schistosoma mansoni cercariae were used in the experiment. Group I included infected untreated control mice. Group II: Subgroup II (a): Animals received 1/3 the dose of praziquantel 25 days post infection. Subgroup II (b): Mice were given 1/3 dose of flubendazole 25 days post infection. Subgroup II (c): Animals received the combination (1/3 dose of flubendazole + 1/3 the dose of praziquantel 25 days post infection. Group III: Subgroup III (a): Mice were given 1/3 the dose of praziquantel 7 weeks post infection. Subgroup III (b): Mice received 1/3 dose of flubendazole 25 days post infection. 24 days later, 1/3 the dose of praziquantel was given. Mice given the consecutive drug regimen (flubendazole 1/3 single oral dose 25 days post infection, then praziquantel 1/3 oral dose for two successive days 24 days later, revealed a significant reduction in the recovery of adult schistosomes after portal perfusion (95.9%), absence of immature stages of ova development, a higher level of dead ova in the oogram and the smallest granuloma mean diameter. These data were less conspicuous in mice given the simultaneous drug regimen.

PP-189 Evaluation of the anthelmintic effects of artemether against experimental Schistosoma mansoni infection in mice using different time periods of treatment

PP-189 Evaluation of the anthelmintic effects of artemether against experimental Schistosoma mansoni infection in mice using different time periods of treatment

Effects of intermediate host genetic background on parasite transmission dynamics: A case study using Schistosoma mansoni

For parasites that require multiple hosts to complete their development, genetic interplay with one host may impact parasite transmission and establishment in subsequent hosts. In this study, we used microsatellite loci to address whether the genetic background of snail intermediate hosts influences life-history traits and transmission patterns of dioecious trematode parasites in their definitive hosts. We performed experimental Schistosoma mansoni infections utilizing two allopatric populations of Biomphalaria glabrata snails and assessed intensities and sex ratios of adult parasites in mouse definitive hosts. Our results suggest that the genetic background of hosts at one point in a parasite’s life cycle can influence the intensities and sex ratios of worms in subsequent hosts.

T Regulatory Cell Levels Decrease in People Infected With Schistosoma mansoni on Effective Treatment

Schistosomiasis mansoni is usually a chronic infection that leads to long-term, systemic exposure to schistosome antigens. Experimental Schistosoma mansoni infection is associated with immunoregulatory mechanisms, including T regulatory cells (Treg) that may help control morbidity and dampen resistance to re-infection. We now show that some schistosomiasis mansoni patients have high proportions of CD3(+)/CD4(+)/CD25(high) Treg. On effective treatment with praziquantel, these high Treg percentages decrease, and fewer of the remaining Treg express CD45RO. The proportion of Treg in S. mansoni-infected patients is inversely related to their percentage of activated, putative effector T cells (CD3(+)/CD4(+)/CD25(medium)/HLA-DR(+) cells). We conclude some, but not all, schistosomiasis mansoni patients develop high percentages of circulating Treg, and effective treatment both decreases the levels of these cells and changes their phenotypes, possibly because of the removal of constant exposure to antigens from intravascular, egg-producing adult worms.

Evaluation of the anthelmintic effects of artesunate against experimental Schistosoma mansoni infection in mice using different treatment protocols

The therapeutic effects of artesunate against experimental Schistosoma mansoni infection in mice were analyzed. Previous studies showed that artesunate is highly effective against S. japonicum infection, but the action of this drug against S. mansoni remained uncovered. The present study examines the optical conditions for artesunate against S. mansoni and evaluates the effects of inhibiting the sexual maturation of adult worms. Mice infected with S. mansoni were orally administered with artesunate according to different schedules. Four consecutive administrations of 300 mg/kg of artesunate at 2-week intervals conferred almost total protection without the development of pathological lesions in the liver. The significant reduction in the number of eggs produced by surviving worms and the status of egg maturation suggested that artesunate inhibits sexual maturation. Electron microscopy revealed that artesunate caused morphological damage, especially on the worm tegument. Artesunate was also very effective in iron-deficient mice. Furthermore, the efficacy of artesunate was equal to or better than that of artemether against S. japonicum infection. Considering that artemether is more toxic, artesunate is currently one of the most efficient drugs against immature S. mansoni.

Meeting report: 4th Biennial Congress of the International Eosinophil Society

There is currently a scientific debate regarding the role ofthe eosinophil in health and disease, in particular inallergic diseases (1–5). Therefore, the 4th biennial meetingof the International Eosinophil Society (May 25–29,2005, Bern, Switzerland) received great attention. Themeeting was organized by Dr H.-U. Simon (Switzerland),and was attended by 150 global participants. The meetinghonored Dr Christopher J. F. Spry, who delivered thefirst Paul Ehrlich Lectureship of the InternationalEosinophil Society for his more than 30 years ofoutstanding contributions to the field of eosinophilresearch.Several new views about the role of these enigmaticcells in immunity and disease emerged. Two differentgenetically engineered eosinophil-deficient mice providedthe basis for a profusion of animated discussions. Usingthese mice, several investigators (J. Lee, Arizona; C.Gerard, Boston; and P. Fulkerson, Cincinnati) demon-strated a critical role for eosinophils in experimentalasthma, yet there was considerable discussion about thespecific parameters of disease pathophysiology affectedby eosinophils, particularly the role of eosinophils inairway hyperreactivity. The role of eosinophils in para-sitic worm infections was reviewed (F. Finkelman,Cincinnati), and a role in controlling hepatotoxicityinduced during experimental Schistosoma mansoni infec-tion (K. Dyer and H. Rosenberg, NIH) was suggestedbased on experiments using eosinophil-deficient mice.Indeed, particular single nucleotide polymorphisms(SNPs) in the eosinophil cationic protein were shown tobe strongly associated with host responses to parasiteinfection (P. Venge, Sweden).Several lines of evidence were presented that eosinoph-ils have an immunoregulatory role involving the produc-tion of substantial levels of cytokines, antigenpresentation (P. Weller, Boston), and targeting of Th1cells for apoptosis via indoleamine 2,3-dioxygenase (IDO)catabolism of tryptophan (R. Moqbel, Canada). A rolefor eosinophils in tissue remodeling and fibrogenesis inexperimental lung fibrosis in mice (S. Phen, Michigan andP. Foster, Australia), human atopy and asthma(A. B. Kay, UK), and human eosinophilic esophagitis(G. Furuta, Boston and A. Straumann, Switzerland) waspresented, including a role for eosinophils in angiogenesisin these processes (F. Levi-Schaffer, Israel). In addition,interactions between eosinophils and nerves were dis-cussed as possible mechanisms for airway hyperreactivityin asthma (R. Costello and M. T. Walsh, Ireland). Theparticipation of eosinophils in innate immunity by directinteraction with various microorganisms including fungi(H. Kita, Rochester, MN, USA) and mycobacteria(M. Capron, France), possibly via Toll-like receptor-2,was presented.Advances in understanding the transcriptional appar-atus responsible for eosinophil lineage-specific geneexpression and development (involving unique doubleGATA-1 transcription factor-binding sites, and thefactors PU.1 and C/EBP

Localization and identification of Schistosoma mansoni/KLH-crossreactive components in infected mice.

KLH (Keyhole limpet hemocyanin) is highly immunogenic, and crossreactive epitopes occur widely in nature. In schistosomiasis, infected hosts generate antibodies reactive with KLH. This is of diagnostic importance but we lack detailed information on the immunogen-carrying molecules and their distribution in the worm. We used anti-KLH antibodies to localize cross-reacting epitopes in the various developmental stages of the parasite in experimental Schistosoma mansoni infection. The staining results show KLH crossreactivity in the life stages of the parasite. By immunoblotting we show that KLH-crossreactive antigenic epitopes in the parasite eggs are carbohydrates, also recognized by antibodies against soluble schistosome egg antigens. The localizations in the larval stages and in adult worms suggest that crossreacting antigenic epitopes are secretory products.

Neuroinflammatory Implication of Schistosoma Mansoni Infection in the Mouse

Schistosomiasis is a parasitic disease due to Schistosoma mansoni. Schistosome infection is known to induce granulomas not only in the spleen, bladder, liver and intestine but also in the brain and spinal cord resulting in severe neuropathological and psychiatric disorders though the interaction between Schistosoma mansoni infection and the nervous system has received on the whole little attention. In the present review it has been discussed recent findings from experimental Schistosoma mansoni infection in mouse nervous system. We show that brain granulomas are associated with a significant alteration in the constitutive levels of nerve growth factor (NGF), a trophic factor playing an essential role in nerve growth and differentiation and in preventing neuronal damages. Animals infected with schistosomes suffered also of increased pain sensitivity which was inhibited by TNF-a antibody injections and not by anti-NGF. These findings suggest that the neuropathological dysfunctions in neuroschistosomiasis may be linked to changes in the basal levels and/or activity of neurotrophic factors caused by local formation of granulomas.