Identification of paramyosin T cell epitopes associated with human resistance to<i>Schistosoma mansoni</i>reinfection

Fonseca, Cristina Toscano; Cunha-Neto, Edécio; Goldberg, Anna Carla; Kalil, Jorge; Jesus, Amélia Ribeiro de; Carvalho, Edgar M.; Correa-Oliveira, Rodrigo; Hammer, Juergen; Sidney, John; Sette, Alessandro; Oliveira, Sérgio C.

doi:10.1111/j.1365-2249.2005.02941.x

Cited by 24 publications

(19 citation statements)

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“…[64]. This, including the positive antibody binding of very small amounts of microfilarial and adult native paramyosin detected herein, suggests that Ol -PARA should be tested as a potential vaccine candidate.…”

Section: Discussionmentioning

confidence: 57%

Paramyosin of canine Onchocerca lupi: usefulness for the diagnosis of a neglected zoonotic disease

et al. 2016

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BackgroundOf increasing importance to the medical and veterinary communities is the zoonotic filarioid nematode Onchocerca lupi. Onchocercosis, thus far found in wolves, dogs, cats and humans, is diagnosed via skin snips to detect microfilariae and surgical removal of adults from the eye of the host. These methods are time-consuming, laborious and invasive, highlighting the need for new tools for the diagnosis of O. lupi in susceptible hosts. Symptoms related to the presence of the adults in the eye can range from none apparent to severe, including blindness. No reliable chemotherapeutic protocols are available, as yet, to eliminate the infection. Paramyosin, an invertebrate-specific protein, has been well-studied as an allergen, diagnostic marker and vaccine candidate. The aim of this study, therefore, was to isolate and characterise paramyosin from O. lupi to assess its suitability for the development of a serological diagnostic assay.MethodsThe adult and microfilarial stages of O. lupi were isolated from the eyes and skin of a 3-year-old male dog. Total RNA was extracted and reverse transcribed into single stranded cDNA. Reverse-transcription PCR was used to isolate a full-length paramyosin cDNA from adult worms and to investigate the temporal expression patterns of this gene. All amplicons were sequenced using dideoxy chain termination sequencing. Bioinformatics was used to predict the amino acid sequence of the gene, to compare the DNA and protein sequences with those available in public databases and to investigate the phylogenetic relationship of all molecules. Antibody binding sites were predicted using bioinformatics and mapped along with published antigenic epitopes against the O. lupi paramyosin protein. The native protein, and three smaller recombinantly expressed peptides, were subjected to western blot using serum from dogs both positive and negative for O. lupi.ResultsParamyosin of O. lupi was herein molecularly characterized, encoded by a transcript of 2,643 bp and producing a protein of 881 amino acids (101.24 kDa). The paramyosin transcript was detected, by reverse transcription PCR, in adults and microfilariae, but not in eggs. Phylogenetic analysis indicates that this molecule clusters with paramyosins from other filarioids to the exclusion of those from other taxa. A total of 621 unique antibody binding epitopes were predicted for this protein and another 28 were conserved in other organisms. This information was used to design three peptides, for recombinant expression, to identify the antibody binding epitope(s) and reduce potential cross-reactivity with serum from dogs infected with other filarioid nematodes. Native paramyosin, purified from microfilariae and adults, was detected by antibodies present in serum from dogs with known O. lupi infections.ConclusionsData provided herein may assist in the development of a serological diagnostic test, based on antibodies to O. lupi paramyosin, for the diagnosis of this infection, in order to gain more information on the real distribution of this l...

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Section: Discussionmentioning

confidence: 57%

Paramyosin of canine Onchocerca lupi: usefulness for the diagnosis of a neglected zoonotic disease

et al. 2016

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“…Pooled odds ratio showed that although there was a positive association of male gender and reinfection with schistosomes, the association was only slightly statistically significant (OR = 1.45, 95% CI = 1.02–2.05, Z = 2.09, p = 0.04). Sensitivity analysis by subgroup analysis based on the species studied showed that statistically significant positive association was observed for association of male gender with reinfection with S. mansoni ( p = 0.02) [25], [28]–[32], [43]–[45] and S. japonicum ( p = 0.002) [24], [42], [46], while the association for reinfection with S. haematobium [26], [34]–[36], [39], [40] was not statistically significant ( p = 0.30) (Figure 3). The exclusion of S. mansoni or S. japonicum subgroups in the meta-analysis yielded effect measures which were not statistically significant ( p = 0.22 and p = 0.23, respectively).…”

Section: Resultsmentioning

confidence: 99%

Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

et al. 2014

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BackgroundSchistosomiasis is still a major public health burden in the tropics and subtropics. Although there is an effective chemotherapy (Praziquantel) for this disease, reinfection occurs rapidly after mass drug administration (MDA). Because the entire population do not get reinfected at the same rate, it is possible that host factors may play a dominant role in determining resistance or susceptibility to reinfection with schistosomes. Here, we systematically reviewed and meta-analyzed studies that reported associations between reinfection with the principal human-infecting species (S. mansoni, S. japonicum and S. haematobium) and host socio-demographic, epidemiological, immunological and genetic factors.Methodology/Principal FindingsPubMed, Scopus, Google Scholar, Cochrane Review Library and African Journals Online public databases were searched in October 2013 to retrieve studies assessing association of host factors with reinfection with schistosomes. Meta-analysis was performed to generate pooled odds ratios and standardized mean differences as overall effect estimates for dichotomous and continuous variables, respectively. Quality assessment of included studies, heterogeneity between studies and publication bias were also assessed. Out of the initial 2739 records, 109 studies were included in the analyses, of which only 32 studies with 37 data sets were eligible for quantitative data synthesis. Among several host factors identified, strong positive association was found with age and pre-treatment intensity, and only slightly for gender. These factors are major determinants of exposure and disease transmission. Significant positive association was found with anti-SWA IgG4 level, and a negative overall effect for association with IgE levels. This reconfirmed the concept that IgE/IgG4 balance is a major determinant of protective immunity against schistosomiasis. Other identified determinants were reported by a small number of studies to enable interpretation.ConclusionsOur data contribute to the understanding of host-parasite interaction as it affects reinfection, and is a potential tool to guide planning and tailoring of community interventions to target high-risk groups.

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“…Epitope prediction was carried out as described previously [52][53][54]. Briefly, the amino acid sequences of SjHSP60 (GenBank accession no.…”

Section: Prediction Of Epitopes and Synthesis Of Peptidesmentioning

confidence: 99%

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

et al. 2009

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Chronic schistosome infection results in the suppression of host immune responses, allowing long-term schistosome survival and restricting pathology. Current theories suggest that Treg play an important role in this regulation. However, the mechanism of Treg induction during schistosome infection is still unknown. The aim of this study was to determine the mechanism behind the induction of CD4 1 CD25 1 T cells by Schistosoma japonicum HSP60 (SjHSP60)-derived peptide SJMHE1 as well as to elucidate the cellular and molecular basis for the induction of CD4 1 CD25 1 T cells during S. japonicum infection. Mice immunized with SJMHE1 or spleen and LN cells from naïve mice pretreated with SJMHE1 in vitro all displayed an increase in CD4 1 CD25 1 T-cell populations. Release of IL-10 and TGF-b by SJMHE1 stimulation may contribute to suppression. Adoptively transferred SJMHE1-induced CD4 1 CD25 1 T cells inhibited delayed-type hypersensitivity in BALB/c mice. Additionally, SJMHE1-treated APC were tolerogenic and induced CD4 1 cells to differentiate into suppressive CD4 1 CD25 1 Treg. Furthermore, our data support a role for TLR2 in SJMHE1-mediated CD4 1 CD25 1 Treg induction. These findings provide the basis for a more complete understanding of the S. japonicum-host interactions that contribute to host homeostatic mechanisms, preventing an excessive immune response.Key words: CD4 1 CD25 1 Treg . Immunomodulation . Schistosomes . SJMHE1 . TLR2 Supporting Information available online IntroductionImmune regulation associated with protective immunity is intricate and entails the effective elimination of the pathogen without causing serious damage to the host. Conversely, effective pathogens have developed multiple mechanisms for modulating or suppressing host immunity as survival and dissemination strategies. Therefore, during the course of an infection, a struggle between host defense mechanisms and the pathogen's immunomodulatory processes results in a complex interplay that may result in pathogen eradication or damage to the host (and persistence of the pathogen). One of the survival strategies used by pathogens involves the induction of immunosuppressive cell populations, e.g. Treg [1,2]. 3052The first observations suggesting that Treg induction occurs during infections with certain pathogens were made in mice infected with Bordetella pertussis [3] and in humans infected with HCV [4] or the nematode Onchocerca volvulus [5]. More recently, Treg induction has been described in chronic infections caused by Candida albicans [6], Mycobacterium tuberculosis [7], HIV [8], Leishmania major [9], Litomosoides sigmodontis [10], and Helicobacter pylori [11]. Treg induction has also been associated with Schistosome infection. Schistosomiasis is a major human disease primarily caused by one of the three species of Schistosome endemic to parts of Asia, South America, and Africa, i.e. S. mansoni, S. haematobium, and S. japonicum. Mortality rates resulting from these types of parasitic infections are second only to malaria. Chronic schis...

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

Cited by 24 publications

References 36 publications

Paramyosin of canine Onchocerca lupi: usefulness for the diagnosis of a neglected zoonotic disease

Paramyosin of canine Onchocerca lupi: usefulness for the diagnosis of a neglected zoonotic disease

Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

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

Cited by 24 publications

References 36 publications

Paramyosin of canine Onchocerca lupi: usefulness for the diagnosis of a neglected zoonotic disease

Paramyosin of canine Onchocerca lupi: usefulness for the diagnosis of a neglected zoonotic disease

Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

CD4+CD25+ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

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CD4⁺CD25⁺ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent