Schistosoma mansoni: Cell-specific expression and secretion of a serine protease during development of cercariae

Fishelson, Zvi; Amiri, Payman; Friend, Daniel S.; Marikovsky, Moshe; Petitt, Matthew; Newport, George; McKerrow, James H.

doi:10.1016/0014-4894(92)90124-s

Cited by 62 publications

(49 citation statements)

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“…We carried out proteomic analysis of the secretions of cercariae stimulated to invade and transform into schistosomula by two independent techniques (4,7,8). In addition to identifying the major protein components released during this initial stage of infection, our analysis provides insights into how "background" protein species can be identified with mass spectrometry technology in a complex "ecosystem" of target organism, snail host, investigator, and laboratory environment.…”

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confidence: 99%

“…First, a carbohydrate-rich surface glycocalyx is released upon entry. This glycocalyx protects the organism from osmotic shock in fresh water but is a potent activator of complement and must be jettisoned prior to entry into the bloodstream (4,5). Second, proteolytic secretions are produced by the set of two groups of acetabular "glands," which are in fact clusters of cells with cytoplasmic processes extending into the anterior end of the organism (6).…”

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confidence: 99%

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Proteomic Analysis of Schistosoma mansoni Cercarial Secretions

Knudsen

Medzihradszky

Lim

et al. 2005

Molecular & Cellular Proteomics

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179

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Schistosomiasis is a global health problem caused by several species of schistosome blood flukes. The initial stage of infection is invasion of human skin by a multicellular larva, the cercaria. We identified proteins released by cercariae when they are experimentally induced to exhibit invasive behavior. Comparison of the proteome obtained from skin lipid-induced cercariae (the natural activator), a cleaner mechanical induction procedure, and an uninduced proteomic control allowed identification of protein groups contained in cercarial acetabular gland secretion versus other sources. These included a group of proteins involved in calcium binding, calcium regulation, and calcium-activated functions; two proteins (paramyosin and SPO-1) implicated in immune evasion; and protease isoforms implicated in degradation of host skin barriers. Several other protein families, traditionally found as cytosolic proteins, appeared concentrated in secretory cells. These included proteins with chaperone activity such as HSP70, -86, and -60. Comparison of the three experimental proteomes also allowed identification of protein contaminants from the environment that were identified because of the high sensitivity of the MS/MS system used. These included proteins from the intermediate host snail in which cercariae develop, the investigator, and the laboratory environment. Identification of proteins secreted by invasive larvae provides important new information for validation of models of skin invasion and immune evasion and aids in rational development of an anti-schistosome vaccine.

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confidence: 99%

mentioning

confidence: 99%

Proteomic Analysis of Schistosoma mansoni Cercarial Secretions

Knudsen

Medzihradszky

Lim

et al. 2005

Molecular & Cellular Proteomics

Self Cite

179

173

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“…In particular, the clusters skin-IgG-C1, skin-IgG-C2, and skin-IgM-C1 showed prolonged antibody response profiles that might be associated with the presence of secretions or material shed into the skin by penetrating cercariae or developing schistosomula, rather than with surface-exposed structures. For S. mansoni, it was shown that skin stage schistosomula still express glycocalyx-related antigens and leave traces in the skin upon further migration to the lungs (43)(44)(45)(46) and that O-glycans expressed by the glycocalyx are quite abundant and antigenic (20,35). However, we observed no significant binding of IgG or IgM from skin ASC probes to the glycocalyx-associated O-glycans that were on the glycan microarray.…”

Section: Discussionmentioning

confidence: 51%

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

et al. 2016

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c Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted Nglycans with terminal mannose residues, Gal␤1-4GlcNAc (LacNAc) and Gal␤1-4(Fuc␣1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAc␤1-4(GlcNAc␤1) n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAc␤1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage-and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection. Schistosomiasis is one of the neglected tropical diseases with the highest impacts on human health. Over 230 million people are infected worldwide, and over 500 million are at risk of infection (1-3). Infection leads to chronic disease characterized by pronounced immunological reactions against eggs deposited into host tissues by the adult schistosome worms, which eventually lead to fibrosis and organ failure (2). Although effective treatment is available, reinfection occurs rapidly and immunity develops only slowly, stressing the need for a prophylactic vaccine as part of a sustainable control strategy (4-6).Schistosomes have a complex life cycle with different life stages that interact with the human host and that each play a role in immunology, immunopathology, and maintenance of infection. Schistosoma infection occurs after direct contact with water containing the larval form of the parasite (cercariae). Cercariae penetrate the host skin and transform into schistosomula, which enter the vasculature and mature while migrating via the lungs to the portal ve...

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“…Ces sécrétions renferment des protéases qui digèrent les macromolécules de la peau [17]. Une sérine protéase isolée à partir d'extraits de cercaires de Schistosoma mansoni possède une activité élastase [32] qui permettrait la dissociation des membranes basales et des tissus conjonctifs [33].…”

Section: Les Protéases De Schistosoma Spunclassified

Les prot�ases chez les helminthes

Trap

Boireau

2000

Vet. Res.

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-Proteases in helmintic parasites. Proteases catalyse the cleavage of internal peptide bonds within peptides and proteins. They are classified into four major classes and are involved in a broad range of eukaryotic processes. Proteases have also been found to play a number of critical roles in the virulence of pathogenic agents, particularly of nematode parasites. Parasitic proteases are involved in different aspects of host-parasite interactions. They facilitate the invasion of host tissues and allow nutrition as well as the survival of the parasite in its host. Proteases also participate in the parasite's evasion from the host's immune response. The functional diversity and complexity of these enzymes are described in this review, with a particular focus on the principally identified proteases of four helminths: Schistosoma sp., Fasciola sp., Taenia sp. and Haemonchus sp. Some of these proteases, especially the cysteine proteases secreted by the parasitic trematode Fasciola hepatica, have been successfully tested in experimental immunodiagnosis. Proteases identified in different parasites are currently under study for a use as recombinant vaccines. In this respect, proteases are proposed as major potential targets for immunotherapy and chemotherapy against parasitic diseases. protease / virulence / helminth / therapy / vaccinationRésumé -Les protéases catalysent le clivage de liaisons peptidiques internes au sein de peptides et protéines. Classées en quatre grandes familles, ces enzymes sont impliquées dans de nombreuses fonctions des cellules eucaryotes. De plus, elles jouent un rôle critique dans la virulence des pathogènes et plus particulièrement des parasites. Elles interviennent à différents niveaux de l'interaction hôte-parasite. Elles facilitent la pénétration du parasite au sein de l'hôte et y assurent sa nutrition ; elles participent également à l'échappement du parasite vis à vis du système immunitaire de l'hôte. La diversité et la complexité fonctionnelle de ces molécules sont illustrées dans cette revue qui décrit les principales protéases identifiées chez quatre helminthes : Schistosoma sp., Fasciola sp., Taenia

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Schistosoma mansoni: Cell-specific expression and secretion of a serine protease during development of cercariae

Cited by 62 publications

References 20 publications

Proteomic Analysis of Schistosoma mansoni Cercarial Secretions

Proteomic Analysis of Schistosoma mansoni Cercarial Secretions

Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

Les prot�ases chez les helminthes

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