Expression of metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in schistosomal portal fibrosis. (33/1591)

Focal extracellular matrix degradation morphologically identified in human portal pipestem fibrosis due to Schistosoma mansoni did not express immunohistochemical reactivity for metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2). However, when active schistosomal periovular granulomas were present, a strong reactivity for MMP-1, MMP-2, TIMP-1, and TIMP-2 was observed. No reactivity was ever observed for MMP-9. However, the positive pattern of immunohistochemical expression was not seen in old fibrotic periovular granulomas, which were sometimes situated in other areas of the same microscopic section. Positive staining for MMPs and TIMPs was observed at the same time in hepatocytes and within the apical portion of bile duct epithelium. These findings are consistent with the concept that matrix degradation in recent and old fibroses, in addition to differing at the ultrastructural level, also differs in immunohistochemical expression of metalloproteinases and their inhibitors.  (+info)

The role of corticosteroids in the treatment of cerebral schistosomiasis caused by Schistosoma mansoni: case report and discussion. (34/1591)

A 26-year-old Brazilian man was admitted to The Toronto Hospital with a headache and visual scintillation. His last travel to Brazil was five years previously. A computed tomography (CT) scan of the head showed an occipital mass with surrounding vasogenic edema. Occipital brain biopsy revealed Schistosoma mansoni eggs. The patient was treated with two doses of praziquantel (20 mg/kg) and dexamethasone (10 mg). His symptoms and occipital mass resolved. Cerebral schistosomiasis is, in part, caused by the host's inflammatory response to Schistosoma. Modes of treatment have included surgical resection, the antiparasitic drugs oxamniquine or praziquantel, and corticosteroids. Corticosteroids may diminish granulomatous inflammation, thereby preventing further tissue destruction, and there is evidence that they also reduce ova deposition. Our review of the literature supports prompt medical therapy in patients with cerebral schistosomiasis. While the minimally or asymptomatic individual may be treated with praziquantel alone, clinicians should consider adjunctive therapy with corticosteroids for patients with prominent neurologic signs or symptoms or mass lesions with evidence of surrounding edema on a CT scan or by magnetic resonance imaging.  (+info)

Toxoplasma gondii and Schistosoma mansoni synergize to promote hepatocyte dysfunction associated with high levels of plasma TNF-alpha and early death in C57BL/6 mice. (35/1591)

To address the question of how the murine host responds to a prototypic type 1 cytokine inducer while concurrently undergoing a helminth-induced type 2 cytokine response, C57BL/6 strain animals with patent schistosomiasis mansoni were orally infected with the cystogenic Toxoplasma gondii strain ME49. Schistosoma mansoni infection resulted in a significantly higher mortality rate when mice were subsequently orally infected with ME49, and these animals displayed a defective IFN-gamma and NO response relative to animals infected with T. gondii alone. Plasma levels of TNF-alpha and aspartate transaminase in double-infected mice were greatly elevated relative to mice infected with either parasite alone. Consistent with the latter observation, these animals exhibited severe liver pathology, with regions of coagulative necrosis and hepatocyte vacuolization unapparent in mice carrying either infection alone. Interestingly, mean egg granuloma size was approximately 50% of that in mice with S. mansoni infection alone. The exacerbated liver pathology in coinfected mice did not appear to be a result of uncontrolled tachyzoite replication, because both parasite-specific RT-PCR analysis and immunohistochemical staining demonstrated a low number of tachyzoites in the liver. We hypothesize that mortality in these animals results from the high level of systemic TNF-alpha, which mediates a severe liver pathology culminating in death of the animal.  (+info)

Intranasal administration of synthetic recombinant peptide-based vaccine protects mice from infection by Schistosoma mansoni. (36/1591)

Schistosomiasis is the cause of a chronic debilitating disease which accounts for significant mortality and morbidity every year, especially in tropical and subtropical areas. An epitope derived from the protective surface protein 9B-Ag of Schistosoma mansoni, designated 9B peptide-1, was previously showed to be protective in mice when conjugated to bovine serum albumin and administered subcutaneously in complete Freund's adjuvant. In this work, this protective peptide was expressed in the flagellin of a Salmonella vaccine strain, and the isolated recombinant flagella were used for immunization of mice. Since during the invasion of the parasite into the host the schistosomula migrate first to the lungs, the intranasal route of administration was employed in order to halt the parasite at an early stage of the infection. Such intranasal immunization with this peptide expressed in flagellin, without the addition of adjuvants, resulted in a significant humoral response and also led to protection against challenge infection, manifested as a reduction of the worm burden by an average of 42%.  (+info)

Polarization of the immune response to the single immunodominant epitope of p38, a major Schistosoma mansoni egg antigen, generates Th1- or Th2-type cytokines and granulomas. (37/1591)

In schistosomiasis mansoni, helminth eggs secrete soluble egg antigens (SEA) that induce T-cell-mediated granulomatous tissue responses. The cloned 38-kDa peptide (p38) of SEA was shown to induce and elicit Th1-type responsiveness in H-2(k) mice. Subsequently, the immunodominant T-cell epitope (P4) of p38 was shown to elicit pulmonary granuloma formation and Th1-type cytokine production in sensitized or infected mice. Here, we report that the immune response to p38 or P4 can be polarized to a Th1 or Th2 profile when the peptides are presented intraperitoneally in soluble recombinant interleukin-12 (IL-12) or alum adjuvant, respectively. The Th1 or Th2 profile was verified by cytokine secretion, enzyme-linked spot assay, and antibody isotype characterization. Importantly, the polarized immune response generated two types of pulmonary granulomas around injected P4-coated beads. The type 1 granulomas were smaller and contained mononuclear cells and occasional thin strands of deposited collagen. In contrast, the type 2 lesions were larger and contained mononuclear cells, large numbers of eosinophils, and several thick bands of deposited collagen. By reverse transcription-PCR cytokine, message in the type 1 granuloma-bearing lungs was found for gamma interferon, tumor necrosis factor alpha, and inducible nitric oxide synthase but not for IL-4 or IL-5. Conversely, lungs with type 2 granulomas had message only for IL-4 and IL-5. These results show that in the proper cytokine environment, the response to a strong Th1 inducer peptide can be deviated to a Th2 profile.  (+info)

Genetic control of schistosome infections by the SM1 locus of the 5q31-q33 region is linked to differentiation of type 2 helper T lymphocytes. (38/1591)

Human susceptibility to Schistosoma mansoni infections is controlled by the SM1 locus on chromosome 5 in q31-q33. This genetic region encodes cytokines which regulate the development of helper T lymphocytes. In the present work, a clonal analysis of CD4(+) T lymphocytes of homozygous resistant and homozygous susceptible subjects was undertaken to evaluate whether SM1 controls helper T-cell differentiation. Of 121 CD4(+) T-cell clones (TCC) from three susceptible (S) and three resistant (R) subjects, 68 proliferated when stimulated by parasite antigens. Parasite-specific TCC derived from susceptible subjects (33 STCC) produced 10- to 1,000-fold less interleukin-4 and -5 than TCC from resistant subjects (25 RTCC). Clones from both patient groups produced, however, the same amount of gamma interferon. Parasite-specific STCC were type 1 helper (Th1) or Th0/1, whereas RTCC were either Th2 or Th0/2. These results, together with the localization of SM1 in 5q31-q33, indicate that the SM1 locus controls the differentiation of Th2 lymphocytes.  (+info)

Schistosomiasis mansoni: immunoblot analysis to diagnose and differentiate recent and chronic infection. (39/1591)

One hundred seven patients classified into three different groups (11 with acute schistosomiasis, 58 with chronic schistosomiasis, and 38 children with high IgM-specific antibody titers against schistosome gut-associated antigens living in an endemic schistosomiasis area) were studied by immunoblotting for the presence of IgG, IgM, and IgA antibodies against Schistosoma mansoni soluble adult worm antigen preparation. We used sera from 15 individuals infected with various intestinal parasites, as well as sera from 19 uninfected individuals, as controls. An immunogenic fraction with a molecular weight of 31-32 kD (Sm31/32) was the most frequently recognized by the different antibody isotypes. In the group with acute disease, this fraction was recognized by IgG and IgM antibodies of all patients, and by 10 (90.9%) of 11 samples for IgA antibodies. Approximately 98% of the patients with chronic infections had IgG antibodies against Sm31/32, but only about 10% had IgM and IgA antibodies against this fraction. The IgG immunoblot profiles of the children from the endemic area were similar to those obtained for the group with acute schistosomiasis. This observation suggests recent infection of these children. Our data show that the Sm31/32 protein fraction is highly immunogenic and may be a useful serologic marker for diagnosing and differentiating between acute and chronic schistosomiasis infection.  (+info)

Blockage of skin invasion by schistosome cercariae by serine protease inhibitors. (40/1591)

Invasion of skin by schistosome cercariae is facilitated by a serine protease secreted from the acetabular cells of cercariae in response to skin lipid. Specific inhibitors of the protease, when applied to human skin in formulations designed to retain the inhibitor on and in the upper stratum corneum layers, block cercarial invasion of human skin. Both peptide-based, irreversible inhibitors and non-peptide, reversible inhibitors block cercarial invasion when applied in a propylene glycol:isopropyl alcohol (3:1) formulation in vitro. Arrest of cercarial invasion could be achieved even after immersion of treated skin in water for 2 hr. Peptide-based irreversible inhibitors in the presence of three different Topicare Delivery Compounds optimized arrest of cercarial invasion. The three Topicare Delivery Compounds applied alone prevented 80-100% of cercarial invasion. With inclusion of the inhibitor, there was 97-100% inhibition in vitro. The optimal formulation with inhibitor was then applied to the tails of BALB/c mice, and the mice were exposed to 120 cercariae by tail immersion. With the carrier lotion alone, there was a 50% reduction in worm burden and a 70% reduction in egg burden. When inhibitor was included, an 80% reduction in worm burden and a 92% reduction in egg burden was observed.  (+info)