The glutathione transferase activity and tissue distribution of a cloned Mr28K protective antigen of Schistosoma mansoni.

Taylor, John B.; Vidal, Alessandra Roseline; Torpier, Gérard; Meyer, David J.; Roitsch, C.; Balloul, Jean‐Marc; Southan, Christopher; Sondermeyer, P.; Pemble, Sally; Lecocq, Jean‐Pierre

doi:10.1002/j.1460-2075.1988.tb02834.x

Cited by 166 publications

(71 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, the mutation of Tyr at position 10 abrogated the PGDS activity of Sm28GST and its ability to impair LC migration, thus confirming the importance of this residue in the enzymatic activity of both mammalian and pathogen-derived PGDS. Altogether, along with its role in parasite survival strategies [34], Sm28GST is also a potent modulator of LC/DC migration during infection. Therefore, inhibition of the enzymatic (GST and PGDS) activities of Sm28GST by neutralizing Ab generated after immunization with the protein, may explain why this Ag is presently considered as an important vaccine candidate against schistosomiasis [35].…”

Section: Discussionmentioning

confidence: 99%

Pivotal roles of the parasite PGD₂ synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

Hervé

Angeli

Pinzar³

et al. 2003

Eur J Immunol

258

View full text Add to dashboard Cite

Prostaglandins (PG) are important modulators of immune and inflammatory responses. We recently demonstrated that the production of PGD 2 by the helminthic parasite Schistosoma mansoni inhibits the migration of epidermal Langerhans cells (LC) to the draining lymph nodes (DLN). Here, we identify the responsible parasite enzyme as being a 28-kDa glutathione-S-transferase (termed Sm28GST). Intradermal injection of Sm28GST in wildtype (WT), but not in D prostanoid receptor (DP) 1-deficient mice abrogates the departure of LC from the epidermis after TNF- § or FITC treatment. During infection, DP1 deficiency restores LC migration, but does not enhance the rate of T cell proliferation in the skin DLN. However, relative to WT mice, DLN cells from DP1-deficient infected mice produce dramatically less IFN-+ and IL-10, but equal amount of IL-4. Interestingly, infected DP1-deficient mice develop a more Th2-biased humoral immune response, a significantly reduced parasitemia and a decreased egg-induced inflammatory response in the liver and intestines. Taken together, we propose that DP1 activation by the Sm28GST-derived PGD 2 could represent a strategy for the schistosome to evade host immune defenses. We also suggest that DP1 is important in the Th1/Th2 balance of the immune response and in inflammatory reactions during infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Pivotal roles of the parasite PGD₂ synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

Hervé

Angeli

Pinzar³

et al. 2003

Eur J Immunol

258

View full text Add to dashboard Cite

show abstract

“…Recently, GSTs have been identified and cloned from Schistosoma japonicum (27) and Schistosoma mansoni (28,29), trematode parasites of man. In the latter case, the enzyme is localized in the external tegument (29), and immunization of rats and mice with recombinant constructs results in a significant level of protection against challenge infection (28).…”

Section: Discussionmentioning

confidence: 99%

Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase.

Cookson

Blaxter

Selkirk

1992

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Lymphatic filariasis is a serious debilitating disease that affects some 90 million people worldwide (1). The causative agents, filarial nematodes of the genera Brugia and Wuchereria, are parasites that persist for long periods of time in the human lymphatic system. They achieve this longevity despite a vigorous host immune response and their apparent inability to undergo antigenic variation, implying a sustained resistance to or subversion of host immunity. All nematodes are bounded by a cuticle, an extracellular matrix composed predominantly of collagens, and a highly cross-linked external envelope of proteins termed cuticlin (2, 3). In contrast to these conserved structural elements, the nematode cuticle exhibits an extremely restricted profile of soluble constituent proteins that may be species-or stagespecific (3, 4). The major protein of adult lymphatic filarial parasites defined by surface labeling is a 29-kDa glycoprotein (gp29) that appears to be expressed after infection of the mammalian host (5-11). Peptide mapping has shown that gp29 from Brugia pahangi and Brugia malayi are highly homologous (8), and the 29-kDa surface-labeled protein from Brugia timori (5) and Wuchereria bancrofti (6) probably represents the same molecule. In adult B. malayi gp29 is synthesized in the syncytial hypodermis, exported to the cuticle, and released into the external environment during in vitro culture (9, 10).We report here the isolation and sequence of cDNAs that encode gp29 from B. pahangi,t which reveals that this cuticular protein is a homolog of the antioxidant enzyme glutathione peroxidase (GSHPx). A possible biological role for this enzyme in defense against immune-mediated cytotoxicity is discussed. MATERIALS AND METHODSParasites. B. malayi were obtained from TRS laboratories, Athens, GA. Adult worms were recovered from the peritoneal cavities ofjirds (Meriones unguiculatus) infected over 3 mo previously with 200 infective larvae and washed extensively with phosphate-buffered saline.Labeling Procedures and Immunochemical Analysis. Adult B. malayi (mixed sex) were extrinsically labeled with BoltonHunter reagent and Iodo-Gen as described elsewhere (12). Parasites were also metabolically labeled with sodium[5S]selenite at 0.25 mCi ml-1 (Amersham SCS-1; 1 Ci = 37 GBq) via in vitro culture for 24 hr in RPMI 1640 medium/2 mM glutamine/1% glucose/penicillin at 100 units-ml-'/ streptomycin at 100 ,ugml-1. All labeled preparations were homogenized in phosphate-buffered saline/1.5% 1-octyl glucoside containing a mixture of protease inhibitors (12) and then centrifuged at 11,000 x g. Immunoprecipitation assays were done with 2.5 ,ul of antiserum in a total volume of 50 ,ul as described (12), resolved on 7-25% gradient polyacrylamide gels, and autoradiographed.cDNA Isolation, Confirmation, and Sequence Determination. A cDNA library in bacteriophage Agtll constructed from mRNA of mixed adult B. pahangi (13) was screened with a polyclonal antiserum to gp29 (9). Clones that reacted positively against gp29 in immunoprecipitatio...

show abstract

“…A 28kDa antigen (Balloul et al 1985), later identified as glutathione-S-transferase (Sm28GST; Taylor et al 1988) and fatty acid binding protein (Sm14; Moser et al 1991) emerged by this route.…”

Section: V) Immunogenicitymentioning

confidence: 99%

Schistosome vaccines: a critical appraisal

Wilson

Coulson

2006

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

The glutathione transferase activity and tissue distribution of a cloned Mr28K protective antigen of Schistosoma mansoni.

Cited by 166 publications

References 28 publications

Pivotal roles of the parasite PGD₂ synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

Pivotal roles of the parasite PGD₂ synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase.

Schistosome vaccines: a critical appraisal

Contact Info

Product

Resources

About

The glutathione transferase activity and tissue distribution of a cloned Mr28K protective antigen of Schistosoma mansoni.

Cited by 166 publications

References 28 publications

Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase.

Schistosome vaccines: a critical appraisal

Contact Info

Product

Resources

About

Pivotal roles of the parasite PGD₂ synthase and of the host D prostanoid receptor 1 in schistosome immune evasion

Pivotal roles of the parasite PGD₂ synthase and of the host D prostanoid receptor 1 in schistosome immune evasion