Differential expression of GP63 genes in Trypanosoma cruzi

Grandgenett, Paul M.; Coughlin, Bridget C.; Kirchhoff, Louis V.; Donelson, John E.

doi:10.1016/s0166-6851(00)00275-9

Cited by 38 publications

(35 citation statements)

References 22 publications

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“…This finding was in agreement with those of previous studies showing that trans-sialidases constitute the dominant group of proteins released by trypomastigotes in infected animals or cell cultures (32,45,62). The gp63 proteases, which are expressed by trypomastigotes and amastigotes (63), as well as several integral membrane proteins with transporter activity (Table S2), were also detected, which is consistent with the hypothesis that T. cruzi vesicles in the TESA preparation are derived primarily from the trypomastigote or amastigote plasma membrane (33,37,64). In addition, TESA EVs also contained a variety of proteins known to localize to the glycosome, flagella, mitochondria, nuclei, or cytosol (Table 1; Table S2), many of which have been previously detected in purified EVs from Leishmania and Trypanosoma brucei (38,41,65).…”

Section: Discussionsupporting

confidence: 92%

Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells

et al. 2017

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Chagas disease, caused by Trypanosoma cruzi, although endemic in many parts of Central and South America, is emerging as a global health threat through the potential contamination of blood supplies. Consequently, in the absence of a gold standard assay for the diagnosis of Chagas disease, additional antigens or strategies are needed. A proteomic analysis of the trypomastigote excreted-secreted antigens (TESA) associated with exosomal vesicles shed by T. cruzi identified ϳ80 parasite proteins, with the majority being trans-sialidases. Mass spectrometry analysis of immunoprecipitation products performed using Chagas immune sera showed a marked enrichment in a subset of TESA proteins. Of particular relevance for diagnostic applications were the retrotransposon hot spot (RHS) proteins, which are absent in Leishmania spp., parasites that often confound diagnosis of Chagas disease. Interestingly, serological screens using recombinant RHS showed a robust immunoreactivity with sera from patients with clinical stages of Chagas ranging from asymptomatic to advance cardiomyopathy and this immunoreactivity was comparable to that of crude TESA. More importantly, no cross-reactivity with RHS was detected with sera from patients with malaria, leishmaniasis, toxoplasmosis, or African sleeping sickness, making this protein an attractive reagent for diagnosis of Chagas disease.

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Section: Discussionsupporting

confidence: 92%

Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells

et al. 2017

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“…1C). Tcgp63-I genes are similar to those previously described (22). Tcgp63-II, on the other hand, represents a new group not described before, composed mainly by tandemly linked genes (Fig.…”

Section: Discussionsupporting

confidence: 77%

“…1A). The Tcgp63-I group presents a high degree of homology with the sequences named gp63-1 to -4 previously identified by Grandgenett et al (22). Tcgp63-Ia protein is 92.4% similar to Tcgp63-Ib and 99.3% to gp63-2.…”

Section: Resultsmentioning

confidence: 55%

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gp63 Homologues inTrypanosoma cruzi: Surface Antigens with Metalloprotease Activity and a Possible Role in Host Cell Infection

2003

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gp63 is a highly abundant glycosylphosphatidylinositol (GPI)-anchored membrane protein expressed predominantly in the promastigote but also in the amastigote stage of Leishmania species. In Leishmania spp., gp63 has been implicated in a number of steps in establishment of infection. Here we demonstrate that Trypanosoma cruzi, the etiological agent of Chagas' disease, has a family of gp63 genes composed of multiple groups. Two of these groups, Tcgp63-I and -II, are present as high-copy-number genes. The genomic organization and mRNA expression pattern were specific for each group. Tcgp63-I was widely expressed, while the Tcgp63-II group was scarcely detected in Northern blots, even though it is well represented in the T. cruzi genome. Western blots using sera directed against a synthetic peptide indicated that the Tcgp63-I group produced proteins of ϳ78 kDa, differentially expressed during the life cycle. Immunofluorescence staining and phosphatidylinositol-specific phospholipase C digestion confirmed that Tcgp63-I group members are surface proteins bound to the membrane by a GPI anchor. We also demonstrate the presence of metalloprotease activity which is attributable, at least in part, to Tcgp63-I group. Since antibodies against Tcgp63-I partially blocked infection of Vero cells by trypomastigotes, a possible role for this group in infection is suggested.

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“…S1 B and C). The third plasmid encoded the NY-ESO-1 gene along with a signal peptide (SP) from a T. cruzi metalloprotease, named glycoprotein 63 (gp63) (21), and used to favor NY-ESO-1 secretion by the parasite (Fig. S1D).…”

Section: Resultsmentioning

confidence: 99%

Trypanosoma cruzias an effective cancer antigen delivery vector

Junqueira

Santos

Galvão-Filho

et al. 2011

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

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One of the main challenges in cancer research is the development of vaccines that induce effective and long-lived protective immunity against tumors. Significant progress has been made in identifying members of the cancer testis antigen family as potential vaccine candidates. However, an ideal form for antigen delivery that induces robust and sustainable antigen-specific T-cell responses, and in particular of CD8 + T lymphocytes, remains to be developed. Here we report the use of a recombinant nonpathogenic clone of Trypanosoma cruzi as a vaccine vector to induce vigorous and longterm T cell-mediated immunity. The rationale for using the highly attenuated T. cruzi clone was (i) the ability of the parasite to persist in host tissues and therefore to induce a long-term antigen-specific immune response; (ii) the existence of intrinsic parasite agonists for Toll-like receptors and consequent induction of highly polarized T helper cell type 1 responses; and (iii) the parasite replication in the host cell cytoplasm, leading to direct antigen presentation through the endogenous pathway and consequent induction of antigenspecific CD8 + T cells. Importantly, we found that parasites expressing a cancer testis antigen (NY-ESO-1) were able to elicit human antigen-specific T-cell responses in vitro and solid protection against melanoma in a mouse model. Furthermore, in a therapeutic protocol, the parasites expressing NY-ESO-1 delayed the rate of tumor development in mice. We conclude that the T. cruzi vector is highly efficient in inducing T cell-mediated immunity and protection against cancer cells. More broadly, this strategy could be used to elicit a long-term T cell-mediated immunity and used for prophylaxis or therapy of chronic infectious diseases.cytokine | prophylaxis | protozoa | innate immunity | Trypanosoma cruzi CL-14

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Differential expression of GP63 genes in Trypanosoma cruzi

Cited by 38 publications

References 22 publications

Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells

Characterization and Diagnostic Application of Trypanosoma cruzi Trypomastigote Excreted-Secreted Antigens Shed in Extracellular Vesicles Released from Infected Mammalian Cells

gp63 Homologues inTrypanosoma cruzi: Surface Antigens with Metalloprotease Activity and a Possible Role in Host Cell Infection

Trypanosoma cruzias an effective cancer antigen delivery vector

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