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Murray E. Selkirk - One of the best experts on this subject based on the ideXlab platform.
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Trichinella spiralis secretes abundant unencapsulated small rnas with potential effects on host gene expression
International Journal for Parasitology, 2020Co-Authors: Peter J Taylor, Murray E. Selkirk, Jana Hagen, Farid N Faruqu, Khuloud T Aljamal, Bonnie Quigley, Morgan Beeby, Peter SarkiesAbstract:Abstract Many organisms, including parasitic nematodes, secrete small RNAs into the extracellular environment, largely encapsulated within small vesicles. Parasite-secreted material often contains microRNAs (miRNAs), raising the possibility that they might regulate host genes in target cells. Here we characterise secreted RNAs from the parasitic nematode Trichinella spiralis at two different life stages. We show that adult T. spiralis, which inhabit intestinal mucosa, secrete miRNAs within vesicles. Unexpectedly, T. spiralis muscle stage larvae, which live intracellularly within skeletal muscle cells, secrete miRNAs that appear not to be encapsulated. Notably, secreted miRNAs include a homologue of mammalian miRNA-31, which has an important role in muscle development. Our work therefore suggests that RNAs may be secreted without encapsulation in vesicles, with implications for the biology of T. spiralis infection.
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Trichinella spiralis secretes abundant unencapsulated small rnas with potential effects on host gene expression
bioRxiv, 2020Co-Authors: Peter J Taylor, Murray E. Selkirk, Jana Hagen, Farid N Faruqu, Khuloud T Aljamal, Bonnie Quigley, Morgan Beeby, Peter SarkiesAbstract:Abstract Many organisms, including parasitic nematodes, secrete small RNAs into the extracellular environment largely encapsulated within small vesicles. Parasite secreted material often contains microRNAs (miRNAs), raising the possibility that they might contribute to pathology by regulating host genes in target cells. Here we characterise material from the parasitic nematode Trichinella spiralis at two different life stages. We show that adult T. spiralis, which inhabit intestinal mucosa, secrete miRNAs within vesicles. Unexpectedly however, T. spiralis muscle stage larvae (MSL), which live intracellularly within skeletal muscle cells, secrete miRNAs that appear not to be encapsulated. Notably, secreted miRNAs include a homologue of mammalian miRNA-31, which has an important role in muscle development. Our work therefore suggests a new potential mechanism of RNA secretion with implications for the pathology of T. spiralis infection.
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characterisation of novel protein families secreted by muscle stage larvae of Trichinella spiralis
International Journal for Parasitology, 2009Co-Authors: David B Guiliano, Kleoniki Gounaris, Yelena Oksov, Sara Lustigman, Murray E. SelkirkAbstract:Proteins secreted by Trichinella spiralis have a potential role in remodelling host skeletal muscle. However, whilst many parasite-secreted proteins have been identified, it has rarely been demonstrated that these are secreted into the nurse cell. Using an informatics-based analysis, we have searched the T. spiralis expressed sequence tag (EST) datasets for cDNAs encoding potential secreted proteins. Here we describe the characterisation of three of the top candidates isolated from our analysis, termed secreted from muscle stage larvae (SML)-1, -2 and -3. All three proteins were demonstrated to be secreted by muscle stage larvae, and immunohistochemical analysis established that SML-1 and -2 are secreted into developing nurse cells. We also show that SML-2 is processed from a precursor into smaller peptides by a metalloprotease contained within T. spiralis-secreted products. With the identification of these and other secreted proteins, we now have molecules to test in functional assays designed to dissect molecular features of the developing nurse cell.
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Secreted variant of nucleoside diphosphate kinase from the intracellular parasitic nematode Trichinella spiralis.
Infection and immunity, 2001Co-Authors: Kleoniki Gounaris, Simon Thomas, Pilar Najarro, Murray E. SelkirkAbstract:The molecular components involved in the survival of the parasitic nematode Trichinella spiralis in an intracellular environment are poorly characterized. Here we demonstrate that infective larvae secrete a nucleoside diphosphate kinase when maintained in vitro. The secreted enzyme forms a phosphohistidine intermediate and shows broad specificity in that it readily accepts γ-phosphate from both ATP and GTP and donates it to all nucleoside and deoxynucleoside diphosphate acceptors tested. The enzyme was partially purified from culture medium by ATP affinity chromatography and identified as a 17-kDa protein by autophosphorylation and reactivity with an antibody to a plant-derived homologue. Secreted nucleoside diphosphate kinases have previously been identified only in prokaryotic organisms, all of them bacterial pathogens. The identification of a secreted variant of this enzyme from a multicellular eukaryote is very unusual and is suggestive of a role in modulating host cell function.
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a reversible protein phosphorylation system is present at the surface of infective larvae of the parasitic nematode Trichinella spiralis
FEBS Letters, 2000Co-Authors: Vincent P Smith, Murray E. Selkirk, Kleoniki GounarisAbstract:Trichinella spiralis infective larvae have externally oriented enzymes catalysing reversible protein phosphorylation on their surface. Incubation of larvae with exogenous ATP resulted in phosphorylation of surface bound and released proteins. Exposure of the parasites to bile, a treatment which renders them infective for intestinal epithelia, resulted in increased release of protein and an altered profile of phosphorylation. Both serine/threonine and tyrosine phosphorylation and dephosphorylation reactions took place at the parasite surface. Examination of the structural characteristics of the larvae following exposure to bile showed that the non-bilayer surface coat was not shed but was structurally reorganised.
Pascal Boireau - One of the best experts on this subject based on the ideXlab platform.
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immune responses in mice vaccinated with a dna vaccine expressing serine protease like protein from the new born larval stage of Trichinella spiralis
Parasitology, 2017Co-Authors: Jing Xu, Libo Wang, Joke Van Der Giessen, Pascal BoireauAbstract:Trichinella spiralis is a parasitic helminth that can infect almost all mammals, including humans. Trichinella spiralis infection elicits a typical type 2 immune responses, while suppresses type 1 immune responses, which is in favour of their parasitism. DNA vaccines have been shown to be capable of eliciting balanced CD4(+) and CD8(+) T cell responses as well as humoral immune responses in small-animal models, which will be advantage to induce protective immune response against helminth infection. In this study, serine protease (Ts-NBLsp) was encoded by a cDNA fragment of new-born T. spiralis larvae, and was inserted after CMV promoter to construct a DNA vaccine [pcDNA3.1(+)-Ts-NBLsp]. Ts-NBLsp expression was demonstrated by immunofluorescence. Sera samples were obtained from vaccinated mice, and they showed strong anti-Ts-NBLsp-specific IgG response. Mice immunized with the pcDNA3.1(+)-Ts-NBLsp DNA vaccine showed a 77.93% reduction in muscle larvae (ML) following challenge with T. spiralis ML. Our results demonstrate that the vaccination with pcDNA3.1(+)-Ts-NBLsp plasmid promoted the balance of type 1 and 2 immune responses and produced a significant protection against T. spiralis infection in mice.
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Influence of adjuvant formulation on inducing immune response in mice immunized with a recombinant serpin from Trichinella spiralis
Parasite Immunology, 2017Co-Authors: X. Bai, Pascal Boireau, M.y. Liu, L. B. Wang, H. N. Shi, J. W. B. Van Der Giessen, X. L. LiuAbstract:Nematodes of the genus Trichinella are one of the most widespread zoonotic pathogens on the world, and they can still cause major public health problems in many parts of the world. Vaccination against the helminth nematode Trichinella could be a good strategy to reduce the risk of human and animal infection. It was our aim to evaluate three adjuvants, which could be used as an efficient vaccine for animals in combination with rTs-Serpin antigen. In this study, BALB/c mice were vaccinated by an intramuscular route with rTs-Serpin antigen from the parasite Trichinella spiralis in combination with three different adjuvant formulations: Montanide ISA201, Montanide IMS 1313 N PR VG and Freund's complete adjuvant/Freund's incomplete adjuvant (FCA/FIA). The dynamics of IgG, IgM, IgE and cytokine production from spleen cells and worm reduction rate of the vaccinated mice were analysed. The results showed that rTs-serpin can induce partial protection against Trichinella larvae challenge in mice, when compared to the FCA-/FIA-formulated vaccination, the IMS1313 plus rTs-serpin mixture showed higher humoral immunity and similar levels of cellular immunity and worm reduction rate. The study suggested that Montanide IMS nanoparticles 1313 are as effective as FCA but less toxic; thus, Montanide IMS nanoparticles 1313 can be used as a good candidate of adjuvant for developing vaccine against Trichinella spiralis.
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characterisation of a high frequency gene encoding a strongly antigenic cystatin like protein from Trichinella spiralis at its early invasion stage
Parasites & Vectors, 2015Co-Authors: Bin Tang, Pascal Boireau, Libo Wang, Mingyuan Liu, Haining Shi, Vasile Cozma, Xiaolei LiuAbstract:Background The intestinal phase is the early invasion stage of Trichinella spiralis (T. spiralis), in which muscle larvae invade intestine epithelial cells and then develop into adult worms to breed newborn larvae. Thus, intestinal infective larvae are first exposed to the immune system of the host, and antigens from the worms may be the earliest marker in the diagnosis of trichinellosis and may contribute to vaccine development to prevent Trichinella infections in pigs.
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modulation of inflammatory bowel disease in a mouse model following infection with Trichinella spiralis
Veterinary Parasitology, 2013Co-Authors: Yueping Zhao, Mingyuan Liu, Xiaocen Wang, Xiaolei Liu, Yong Yang, H B Zou, S M Sun, Benjamin M Rosenthal, Haining Shi, Pascal BoireauAbstract:Infection of mice with Trichinella spiralis redirects the mucosal immune system from a Th1 to a protective Th2 response with a reduction in the severity of trinitrobenzesulfonic acid-induced colonic damage. T. spiralis infection induced IL-10 production in a dose-dependent manner in oxazolone (OXZ)-induced colitis. This phenomenon may be responsible for the lack of efficacy of T. spiralis in the treatment of OXZ-induced colitis. These results indicate that if the source of increased IL-10 production is identified and addressed, T. spiralis may alter the Th2 response.
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an anti tumor protein produced by Trichinella spiralis induces apoptosis in human hepatoma h7402 cells
Veterinary Parasitology, 2013Co-Authors: Xiaocen Wang, Pascal Boireau, Mingyuan Liu, Xiaolei Liu, S M Sun, Benjamin M Rosenthal, Haining Shi, X R Wang, L X Chu, F WangAbstract:Abstract Trichinella spiralis infection confers effective resistance to tumor cell expansion. In this study, a T7 phage cDNA display library was constructed to express genes encoded by T. spiralis . Organic phase multi-cell screening was used to sort through candidate proteins in a transfected human chronic myeloid leukemia cell line (K562) and a human hepatoma cell line (H7402) using the display library. The protein encoded by the A200711 gene was identified and analyzed using protein analysis software. To test the antitumor effects of A200711, variations in cell proliferation and apoptosis were monitored after recombinant pEGFP-N1-A200711 was transfected into H7402 cells. The results show that the expressed target gene successfully induced apoptosis in H7402 cells as measured by Hoechst-PI staining, MTT assay ( p
Lilian Yepezmulia - One of the best experts on this subject based on the ideXlab platform.
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analysis of the effect of a 2 trifluoromethyl 1h benzimidazole derivative on Trichinella spiralis muscle larvae
Veterinary Parasitology, 2013Co-Authors: Felix Matadamasmartinez, Benjamin Noguedatorres, Francisco Hernandezluis, Guillermo Mendoza, Gabriela Andresantonio, Lilian YepezmuliaAbstract:Albendazole and mebendazole are widely used in the treatment of trichinellosis; however, chemotherapy failure has been reported. In an effort to develop new anthelminthic compounds, we examined a previously synthesized 2-(trifluoromethyl)-1H-benzimidazole derivative (1) that showed good in vitro activity against Trichinella spiralis muscle larvae but low in vivo efficacy. In order to improve the solubility of compound 1, an inclusion complex with 2-hydroxypropyl-β-cyclodextrin (1/HP-βCD) was prepared. When 1/HP-βCD was tested in vivo, it significantly reduced the ML burden (84%). In addition, a proteomic analysis of T. spiralis ML treated with 1 revealed significant changes in the expression levels of proteins involved in energy metabolism and the cytoskeleton of the parasite. Compound (1) also induced extensive ultrastructural changes in the cuticle, hypodermis and midgut of the parasite.
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synthesis and biological activity of 2 trifluoromethyl 1h benzimidazole derivatives against some protozoa and Trichinella spiralis
ChemInform, 2010Co-Authors: Francisco Hernandezluis, Alicia Hernandezcampos, Gabriel Navarretevazquez, Rafael Castillo, Olivia Soriaarteche, Manuel Hernandezhernandez, Lilian YepezmuliaAbstract:Title compounds (I) are evaluated in vitro against various protozoan parasites (Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis, Leishmania mexicana) and the nematode Trichinella spiralis.
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synthesis and biological activity of 2 trifluoromethyl 1h benzimidazole derivatives against some protozoa and Trichinella spiralis
European Journal of Medicinal Chemistry, 2010Co-Authors: Francisco Hernandezluis, Alicia Hernandezcampos, Gabriel Navarretevazquez, Rafael Castillo, Olivia Soriaarteche, Manuel Hernandezhernandez, Lilian YepezmuliaAbstract:A series of 2-(trifluoromethyl)-1H-benzimidazole derivatives (1ae1i) were synthesized via Phillips cyclocondensation of a substituted 1,2-phenylenediamine and trifluoroacetic acid. The synthesized compounds were evaluated in vitro against various protozoan parasites: Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis and Leishmania mexicana, and they showed nanomolar activities against the first three protozoa tested. The compounds were also tested in vitro and in vivo against the nematode Trichinella spiralis. Compounds 1b, 1c and 1e had the most desirable in vitro antiparasitic profile against all parasites studied. In the in vivo model against T. spiralis, compounds 1b and 1e showed good activity against the adult phase at 75 mg/Kg. However, against the muscle larvae stage, only compound 1f exhibited in vivo antiparasitic efficacy.
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detection of Trichinella spiralis muscle larvae in naturally infected horses
Journal of Parasitology, 1995Co-Authors: C Arriaga, Lilian Yepezmulia, N Viveros, L A Adame, E Benitez, Dante S. Zarlenga, M G OrtegapierresAbstract:: Human trichinellosis outbreaks related to horsemeat consumption have been reported in France and Italy in recent years. In order to determine if Trichinella is present in horses slaughtered at an abattoir in the State of Mexico, diaphragm muscle tissue samples (22-37 g) from 80 horses were examined by artificial digestion. Four of these samples had larvae that were characterized as Trichinella sp. by morphological criteria and as Trichinella spiralis by the polymerase chain reaction.
Ljiljana Sofronicmilosavljevic - One of the best experts on this subject based on the ideXlab platform.
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Trichinella spiralis muscle larvae release extracellular vesicles with immunomodulatory properties
Parasite Immunology, 2019Co-Authors: Maja Kosanovic, Jelena Cvetkovic, Alisa Grudenmovsesijan, Milanovic Svetlana, Sasa Vasilev, Natasa Ilic, Ljiljana SofronicmilosavljevicAbstract:AIMS: Extracellular vesicles (EVs) represent a newly discovered but universal communication tool between cells or organisms. However, few data exist on nematode EVs and none for Trichinella spiralis. Here, we aimed to investigate whether T spiralis muscle larvae produce EVs, whether they carry immunomodulatory proteins and whether they have a role in immunomodulation as a component of excretory-secretory muscle larvae products (ES L1). METHODS AND RESULTS: EVs were enriched from conditioned medium of T spiralis muscle larvae. Transmission electron microscopy images showed T spiralis EVs to be 30-80 nm in size, and Western blot confirmed the presence of two out of three glycoproteins with the immunodominant epitope characteristic for muscle larvae of the genus Trichinella. Using a peripheral blood mononuclear cell (PBMC) stimulation assay, it was shown that these EVs elevated production of IL10 and IL6. CONCLUSION: T spiralis muscle larvae produce EVs. Those EVs carry immunomodulatory proteins and have the capacity independently to induce regulatory responses in the same way as the T spiralis excretory-secretory muscle larvae products from which they were isolated.
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immunomodulatory potential of particular Trichinella spiralis muscle larvae excretory secretory components
International Journal for Parasitology, 2016Co-Authors: Jelena Cvetkovic, Ljiljana Sofronicmilosavljevic, Milan Gnjatović, Isao Nagano, Natasa Ilic, Alisa GrudenmovsesijanAbstract:Abstract Excretory–secretory antigens of Trichinella spiralis muscle larvae can induce the semi-matured status of rat dendritic cells. This may at least partly be the consequence of transient activation of extracellular signal-regulated kinases 1/2 (ERK1/2). Here we investigated the potential of several components of excretory–secretory antigens (native fraction containing 45, 49 and 53 kDa proteins and recombinant Tsp53, representing one of the constituents of this fraction) to demonstrate previously observed effects of excretory–secretory antigens on dendritic cells in vitro, characterised by establishment of a particular phenotype (very low MHC II expression, moderate CD86 expression and significant ICAM-1 expression) and functional properties (low production of pro-inflammatory cytokine IL-12p70, and high production of IL-10 and TGF-β). Dendritic cells activated by these components were able to provoke proliferation of naive T cells and their polarisation towards Th2 and anti-inflammatory responses. The investigated antigens had almost the same capacity to induce IL-4 and IL-10 production from T cells as excretory–secretory antigens, but failed to induce significant TGF-β synthesis. It could be concluded that the investigated excretory–secretory antigens components can largely reproduce the immunomodulatory effects of the complete excretory–secretory antigens and therefore may be considered as molecules important for creation of the anti-inflammatory milieu achieved by the parasite.
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lectin blot analyses of Trichinella spiralis muscle larvae excretory secretory components
Parasitology Research, 2002Co-Authors: Alisa Grudenmovsesijan, Natasa Ilic, Ljiljana SofronicmilosavljevicAbstract:The rapid recognition of invading pathogen polysaccharides by host lectins might have a significant role in the outcome of the infection. Oligosaccharide structures of the pathogens may provoke an antibody response and serve as a target for specific antibodies. It is well known that Trichinella spiralis antigens, either on the surface or excreted-secreted, are key modulators or targets of the host immune system. In our study of the role of lectins in host defense against T. spiralis infection, an investigation on sugar component of parasite glycoproteins was performed. Affino-blot analyses of T. spiralis muscle larvae excretory-secretory (ES) products by plant lectins revealed that these proteins possess: (1) N-glycans (ConA, PSA, PHA), and probably some O-linked structures (AAA), (2) oligosaccharide structures with mannose residues, especially of the oligomannose type (ConA) and the biantennary complex type with Fuc in the pentasaccharide core (PSA), (3) bisected oligosaccharides, probably some polyantennary glycophorms (PHA), (4) terminally positioned Gal (RCA I, AAA), (5) N-glycans containing oligomers of, or bisected GlcNAc (WGA), that lack α2,6 type of linkage (absence of SNA binding).
Alisa Grudenmovsesijan - One of the best experts on this subject based on the ideXlab platform.
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Trichinella spiralis muscle larvae release extracellular vesicles with immunomodulatory properties
Parasite Immunology, 2019Co-Authors: Maja Kosanovic, Jelena Cvetkovic, Alisa Grudenmovsesijan, Milanovic Svetlana, Sasa Vasilev, Natasa Ilic, Ljiljana SofronicmilosavljevicAbstract:AIMS: Extracellular vesicles (EVs) represent a newly discovered but universal communication tool between cells or organisms. However, few data exist on nematode EVs and none for Trichinella spiralis. Here, we aimed to investigate whether T spiralis muscle larvae produce EVs, whether they carry immunomodulatory proteins and whether they have a role in immunomodulation as a component of excretory-secretory muscle larvae products (ES L1). METHODS AND RESULTS: EVs were enriched from conditioned medium of T spiralis muscle larvae. Transmission electron microscopy images showed T spiralis EVs to be 30-80 nm in size, and Western blot confirmed the presence of two out of three glycoproteins with the immunodominant epitope characteristic for muscle larvae of the genus Trichinella. Using a peripheral blood mononuclear cell (PBMC) stimulation assay, it was shown that these EVs elevated production of IL10 and IL6. CONCLUSION: T spiralis muscle larvae produce EVs. Those EVs carry immunomodulatory proteins and have the capacity independently to induce regulatory responses in the same way as the T spiralis excretory-secretory muscle larvae products from which they were isolated.
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immunomodulatory potential of particular Trichinella spiralis muscle larvae excretory secretory components
International Journal for Parasitology, 2016Co-Authors: Jelena Cvetkovic, Ljiljana Sofronicmilosavljevic, Milan Gnjatović, Isao Nagano, Natasa Ilic, Alisa GrudenmovsesijanAbstract:Abstract Excretory–secretory antigens of Trichinella spiralis muscle larvae can induce the semi-matured status of rat dendritic cells. This may at least partly be the consequence of transient activation of extracellular signal-regulated kinases 1/2 (ERK1/2). Here we investigated the potential of several components of excretory–secretory antigens (native fraction containing 45, 49 and 53 kDa proteins and recombinant Tsp53, representing one of the constituents of this fraction) to demonstrate previously observed effects of excretory–secretory antigens on dendritic cells in vitro, characterised by establishment of a particular phenotype (very low MHC II expression, moderate CD86 expression and significant ICAM-1 expression) and functional properties (low production of pro-inflammatory cytokine IL-12p70, and high production of IL-10 and TGF-β). Dendritic cells activated by these components were able to provoke proliferation of naive T cells and their polarisation towards Th2 and anti-inflammatory responses. The investigated antigens had almost the same capacity to induce IL-4 and IL-10 production from T cells as excretory–secretory antigens, but failed to induce significant TGF-β synthesis. It could be concluded that the investigated excretory–secretory antigens components can largely reproduce the immunomodulatory effects of the complete excretory–secretory antigens and therefore may be considered as molecules important for creation of the anti-inflammatory milieu achieved by the parasite.
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lectin blot analyses of Trichinella spiralis muscle larvae excretory secretory components
Parasitology Research, 2002Co-Authors: Alisa Grudenmovsesijan, Natasa Ilic, Ljiljana SofronicmilosavljevicAbstract:The rapid recognition of invading pathogen polysaccharides by host lectins might have a significant role in the outcome of the infection. Oligosaccharide structures of the pathogens may provoke an antibody response and serve as a target for specific antibodies. It is well known that Trichinella spiralis antigens, either on the surface or excreted-secreted, are key modulators or targets of the host immune system. In our study of the role of lectins in host defense against T. spiralis infection, an investigation on sugar component of parasite glycoproteins was performed. Affino-blot analyses of T. spiralis muscle larvae excretory-secretory (ES) products by plant lectins revealed that these proteins possess: (1) N-glycans (ConA, PSA, PHA), and probably some O-linked structures (AAA), (2) oligosaccharide structures with mannose residues, especially of the oligomannose type (ConA) and the biantennary complex type with Fuc in the pentasaccharide core (PSA), (3) bisected oligosaccharides, probably some polyantennary glycophorms (PHA), (4) terminally positioned Gal (RCA I, AAA), (5) N-glycans containing oligomers of, or bisected GlcNAc (WGA), that lack α2,6 type of linkage (absence of SNA binding).
