Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection

Corrêa-Oliveira, Rodrigo; Malaquias, Luiz Cosme Cotta; Falcão, Patrícia Lima; Viana, Iramaya R. C.; Bahia-Oliveira, Lilian M. G.; Silveira, Alda Maria Soares; Fraga, Lucia Alves Oliveira; Prata, Áluízio; Coffman, R. L.; Lambertucci, José Roberto; Cunha-Melo, José Renan; Martins‐Filho, Olindo Assis; Wilson, R. A.; Gazzinelli, Giovanni

doi:10.1590/s0100-879x1998000100024

Cited by 67 publications

(66 citation statements)

References 23 publications

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“…Therefore, PGE 2 -driven IL-10 production in the skin following infection may play a significant role in the immunomodulation of inflammatory responses in the skin of infected animals. These findings are similar to those reported by Hoffmann et al (32), who state that a major consequence of schistosome-induced IL-10 production is to 3,125.50 Ϯ 213.5 * Con A ϩ keratinocyte supernatant (50 g/ml) 2,214.10 Ϯ 102.4 * Con A ϩ 14 g/ml fraction IV ϩ 10 g/ml anti-IL- 10 10,987.78 Ϯ 321.8 Con A ϩ 50 g/ml keratinocyte sup ϩ 10 g/ml anti-IL- 10 12,596.14 Ϯ 457.0 down-regulate the immune responses of the host against the parasite. However, this subdued inflammation is seen only so long as live parasites are present in the skin (3), suggesting that the PGE 2 / IL-10-inducing activity is present only in the secretions of the tissue-migrating parasites.…”

Section: Discussionsupporting

confidence: 90%

“…It is baffling, especially in immunized animals, how the skin-stage schistosomula are able to induce an overbearing IL-10 response in a milieu predominated by IFN-␥-producing cells (4 -7). IL-10 has been implicated in the down-regulation of various immune responses against S. mansoni in both mice (8,9) and humans (10,11). Therefore, it is possible that this early IL-10 response in the skin and draining lymph nodes may play a pivotal role in parasite establishment by modulating the Th1-type responses (11,12).…”

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confidence: 99%

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A Role for Parasite-Induced PGE2 in IL-10-Mediated Host Immunoregulation by Skin Stage Schistosomula ofSchistosoma mansoni

Kalyanasundaram

Kumar

2000

The Journal of Immunology

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Significant quantities of PGE2 were produced by cercariae of Schistosoma mansoni following incubation with linoleic acid, a free fatty acid found on the surface of the skin. Cyclooxygenase (COX) 2 inhibitors failed to block this PGE2 production, suggesting that a different biochemical pathway may be involved in the production of PGE2 by the parasite. In addition, the parasites were also able to induce PGE2 and IL-10 from human and mouse keratinocytes. Analysis of mouse skin during skin migratory phases of infection confirmed these in vitro observations. COX2 inhibitors blocked the parasite-induced PGE2 and IL-10 from keratinocytes. Further analysis of the parasite secretions showed that the PGE2/IL-10-inducing effect was associated with a fraction <30 kDa molecular size. Addition of this fraction or parasite-stimulated keratinocyte culture supernatant to Con A-stimulated spleen cells resulted in the suppression of cell proliferation. This effect could be blocked by anti-IL-10 treatment. In sharp contrast, attenuation of the parasites with γ-irradiation significantly abrogated their ability to induce PGE2 or IL-10 from skin cells. Significance of IL-10 in host immunoregulation by skin stage schistosomula of S. mansoni was further confirmed by using IL-10-deficient mice. In these mice the normal subdued cutaneous reaction to the parasite was absent. Instead, a prominent cellular reaction occurred around the parasite, and there was considerable delay in parasitic migration through the skin. Thus these results suggest a key role for parasite-induced PGE2 in IL-10-dependent down-regulation of host immune responses in the skin.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

A Role for Parasite-Induced PGE2 in IL-10-Mediated Host Immunoregulation by Skin Stage Schistosomula ofSchistosoma mansoni

Kalyanasundaram

Kumar

2000

The Journal of Immunology

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“…The selected group lives in the endemic area of Virgem das Graças, state of Minas Gerais (MG), Brazil. After several stool examinations by the Kato-Katz method and negative findings over years of studies, these patients had been referred to as "normal endemic" (Corrêa-Oliveira et al 1998, Gazzinelli et al 2006. The saline gradient method identified a positive infection rate for S. mansoni of 25% based on analysis of two faecal samples of 500 mg. On the other hand, two sets of 12 Kato-Katz slides per each individual revealed a prevalence of 20% of infection.…”

Section: Discussionmentioning

confidence: 99%

Use of a saline gradient for the diagnosis of schistosomiasis

Coelho

Jurberg

Oliveira

et al. 2009

Mem. Inst. Oswaldo Cruz

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Faecal exams are widely used for the diagnosis of intestinal helminth infections because microscopic findings of parasitic structures typically assure reliable and accurate identification of the parasites. Although several types of qualitative and quantitative methods exist for stool examination (Lutz 1919, Hastings-Willis 1921, Faust & Melency 1924, Hoffman et al. 1934, Stoll 1946, Ritchie 1948, Sapero et al. 1951, Kato & Miura 1954, Blagg et al. 1955, Bell 1963, Katz et al. 1972, some of these techniques have operational limitations, including high cost, complexity, low sensitivity and/or reproducibility. These limitations may restrict their respective uses in large-scale surveys in the field.A method commonly used in epidemiological studies due to its relative simplicity and low cost is the quantitative Kato-Katz faecal smear technique (Katz et al. 1972). Katz et al. (1970) showed the limit of sensitivity for this method to be 20 eggs per gram of faeces by recovering Schistosoma mansoni eggs that were added to negative human faecal samples. This exam is considered to be the gold standard for diagnosing schistosomiasis mansoni as per the World Health Organization (WHO 1993). Although this method is widely used, the Kato-Katz test might lack sensitivity in situations of low worm burden, low endemicity and in cases of evaluation post treatment (Ferrari et al. 2003). To overcome these limitations, it is necessary to increase the number of stool samples, which may increase costs and possibly cause logistic difficulties in epidemiological surveys (Enk et al. 2008).Alternative approaches based on antibody, antigen and DNA detection are of potential application, but when the financial and infrastructural difficulties of most endemic countries are taken into consideration, these techniques become unsatisfactory (WHO 2006b). Perhaps as an opposite effect of successful control programs worldwide, the diagnosis of schistosomiasis still needs a more sensitive and low-cost tool for detecting light infections in the field (WHO 2006a). Recently, two novel methods have been proposed. Teixeira et al. (2007) developed a highly sensitive method (named Helmintex) for identifying S. mansoni eggs in large amounts of faeces. Faecal samples of 30 g were processed through a sequence of spontaneous sedimentation, sieving and the Ritchie method and then incubated with or without lectins. This was followed by isolation through interaction with paramagnetic beads and microscopic inspection. The other method consists of a hatching device containing a collecting container for the detection of miracidia (Jurberg et al. 2008). Although hatching methods are highly sensitive, they have an obvious limitation because the faecal samples must be fresh at the moment of the exam. On the other hand, the miracidia suspension fixed in 10% formaldehyde solution could be examined for at least 15 days after the fixation without a statistically significant loss of the miracidia number.In an attempt to develop more sensitive diagnostic tools for schistosomia...

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“…This assay showed that Para (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), Para (210-226) and Para (355-371) were able to bind to 100% (8/8) of the HLA-DR molecules used in this assay,…”

Section: Paramyosin Peptide Binding To Mhc Class II Moleculesmentioning

confidence: 90%

“…A recent study performed with mice infected with S. mansoni has shown that chronic infection is related to IL-10 production, which can be responsible for the Th2 type of immune response observed after egg deposition [25]. IL-10 mediates IFN-γ suppression in human schistosomiasis, and therefore T cell proliferative responses to S. mansoni antigens in infected individuals are reduced [26]. However, we believe that preferential recognition of Para (210-226) by the RR group compared to the SR group cannot be attributed to immunomodulation mediated by IL-10 produced by the SR group, as no statistically significant difference was observed between both groups regarding proliferative responses to PHA.…”

mentioning

confidence: 99%

Identification of paramyosin T cell epitopes associated with human resistance toSchistosoma mansonireinfection

Fonseca

Cunha-Neto

Goldberg

et al. 2005

Clinical and Experimental Immunology

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SummaryParamyosin, a Schistosoma mansoni myoprotein associated with human resistance to infection and reinfection, is a candidate antigen to compose a subunit vaccine against schistosomiasis. In this study, 11 paramyosin peptides selected by TEPITOPE algorithm as promiscuous epitopes were produced synthetically and tested in proliferation and in vitro human leucocyte antigen (HLA)-DR binding assays. A differential proliferative response was observed in individuals resistant to reinfection compared to individuals susceptible to reinfection in response to Para (210-226) peptide stimulation. In addition, this peptide was able to bind to all HLA-DR molecules tested in HLA-DR binding assays, confirming its promiscuity. Para (6-22) and Para (355-371) were also shown to be promiscuous peptides, because they were able to bind to the six and eight most prevalent HLA-DR alleles used in HLA-DR binding assays, respectively, and were also recognized by T cells of the individuals studied. These results suggest that these paramyosin peptides are promising antigens to compose an anti-schistosomiasis vaccine.

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Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection

Cited by 67 publications

References 23 publications

A Role for Parasite-Induced PGE2 in IL-10-Mediated Host Immunoregulation by Skin Stage Schistosomula ofSchistosoma mansoni

A Role for Parasite-Induced PGE2 in IL-10-Mediated Host Immunoregulation by Skin Stage Schistosomula ofSchistosoma mansoni

Use of a saline gradient for the diagnosis of schistosomiasis

Identification of paramyosin T cell epitopes associated with human resistance toSchistosoma mansonireinfection

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