A Subset of Proteins Found in Culture Supernatants of Candida albicans Includes the Abundant, Immunodominant, Glycolytic Enzyme Enolase

Sundstrom, Paula; Aliaga, George R.

doi:10.1093/infdis/169.2.452

Cited by 59 publications

(72 citation statements)

References 14 publications

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“…We have also recently shown that the host response towards Giardia of differentiated Caco-2 cells is partly mediated by soluble factor(s) [8]. The secreted proteins we identify here are immunodominant in human infections [29,36] and experimental mouse infections [13]. The targeting of secreted giardial proteins for immunoneutralization may thus represent a useful therapeutic strategy, aimed at treating or preventing Giardia infections.…”

Section: Discussionmentioning

confidence: 68%

“…Enolase has been implicated in the pathogenesis of other microbes colonizing mucosal surfaces [29,36]; prokaryotic Streptococcus agalactiae, S. sobrinus, S. pyogenes and eukaryotic Candida albicans ␣-enolases are secreted [36,37], while other enolases are surface-associated [29,38,39]. Some of these enolases are immunodominant [29,36], as is Giardia enolase [24,25]. However, we were not able to show any specific activity of secreted Giardia enolase and its direct role, if any, during host-parasite interactions remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

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Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells

Ringqvist

Palm

Skarin

et al. 2008

Molecular and Biochemical Parasitology

154

139

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Giardia lamblia, an important cause of diarrheal disease, resides in the small intestinal lumen in close apposition to epithelial cells. Since the disease mechanisms underlying giardiasis are poorly understood, elucidating the specific interactions of the parasite with the host epithelium is likely to provide clues to understanding the pathogenesis. Here we tested the hypothesis that contact of Giardia lamblia with intestinal epithelial cells might lead to release of specific proteins. Using established co-culture models, intestinal ligated loops and a proteomics approach, we identified three G. lamblia proteins (arginine deiminase, ornithine carbamoyl transferase and enolase), previously recognized as immunodominant antigens during acute giardiasis. Release was stimulated by cell-cell interactions, since only small amounts of arginine deiminase and enolase were detected in the medium after culturing of G. lamblia alone. The secreted G. lamblia proteins were localized to the cytoplasm and the inside of the plasma membrane of trophozoites. Furthermore, in vitro studies with recombinant arginine deiminase showed that the secreted Giardia proteins can disable host innate immune factors such as nitric oxide production. These results indicate that contact of Giardia with epithelial cells triggers metabolic enzyme release, which might facilitate effective colonization of the human small intestine. a b s t r a c tGiardia lamblia, an important cause of diarrheal disease, resides in the small intestinal lumen in close apposition to epithelial cells. Since the disease mechanisms underlying giardiasis are poorly understood, elucidating the specific interactions of the parasite with the host epithelium is likely to provide clues to understanding the pathogenesis. Here we tested the hypothesis that contact of Giardia lamblia with intestinal epithelial cells might lead to release of specific proteins. Using established co-culture models, intestinal ligated loops and a proteomics approach, we identified three G. lamblia proteins (arginine deiminase, ornithine carbamoyl transferase and enolase), previously recognized as immunodominant antigens during acute giardiasis. Release was stimulated by cell-cell interactions, since only small amounts of arginine deiminase and enolase were detected in the medium after culturing of G. lamblia alone. The secreted G. lamblia proteins were localized to the cytoplasm and the inside of the plasma membrane of trophozoites. Furthermore, in vitro studies with recombinant arginine deiminase showed that the secreted Giardia proteins can disable host innate immune factors such as nitric oxide production. These results indicate that contact of Giardia with epithelial cells triggers metabolic enzyme release, which might facilitate effective colonization of the human small intestine.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells

Ringqvist

Palm

Skarin

et al. 2008

Molecular and Biochemical Parasitology

154

139

View full text Add to dashboard Cite

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“…is not exposed at the cell surface (3,51), and phosphoglycerate kinase has been detected at the cell surface of C. albicans cells and has also been detected to extend through the cell wall (2).…”

Section: Resultsmentioning

confidence: 99%

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is a surface antigen

et al. 1997

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A gt11 cDNA library from Candida albicans ATCC 26555 was screened by using pooled sera from two patients with systemic candidiasis and five neutropenic patients with high levels of anti-C. albicans immunoglobulin M antibodies. Seven clones were isolated from 60,000 recombinant phages. The most reactive one contained a 0.9-kb cDNA encoding a polypeptide immunoreactive only with sera from patients with systemic candidiasis. The whole gene was isolated from a genomic library by using the cDNA as a probe. The nucleotide sequence of the coding region showed homology (78 to 79%) to the Saccharomyces cerevisiae TDH1 to TDH3 genes coding for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and their amino acid sequences showed 76% identity; thus, this gene has been named C. albicans TDH1. A rabbit polyclonal antiserum against the purified cytosolic C. albicans GAPDH (polyclonal antibody [PAb] anti-CA-GAPDH) was used to identify the GAPDH in the ␤-mercaptoethanol extracts containing cell wall moieties. Indirect immunofluorescence demonstrated the presence of GAPDH at the C. albicans cell surface, particularly on the blastoconidia. Semiquantitative flow cytometry analysis showed the sensitivity of this GAPDH form to trypsin and its resistance to be removed with 2 M NaCl or 2% sodium dodecyl sulfate. The decrease in fluorescence in the presence of soluble GAPDH indicates the specificity of the labelling. In addition, a dose-dependent GAPDH enzymatic activity was detected in intact blastoconidia and germ tube cells. This activity was reduced by pretreatment of the cells with trypsin, formaldehyde, and PAb anti-CA-GAPDH. These observations indicate that an immunogenic, enzymatically active cell wall-associated form of the glycolytic enzyme GAPDH is found at the cell surface of C. albicans cells.

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“…It will be important to characterize the a-enolase epitopes responsible for T cell reactivity in PDAC to improve their recognition and activation. In this respect, studies with C. albicans and C. tropicalis have identified cytosolic a-enolase as an immunodominant antigen, [44][45][46][47] and Sato et al described a single HLA-DR-restricted peptide of human aenolase identified in squamous cell carcinoma that elicited cytotoxic activity by CD4 T cells. 48 Our data suggest that a-enolase is recognized in the context of HLA-A2 allele.…”

Section: Discussionmentioning

confidence: 99%

An integrated humoral and cellular response is elicited in pancreatic cancer by α‐enolase, a novel pancreatic ductal adenocarcinoma‐associated antigen

Cappello¹,

Tomaino²,

Chiarle³

et al. 2009

Intl Journal of Cancer

107

125

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Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5-year survival rate. a-Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation of its expression with tumor status has been reported for lung and hepatocellular carcinoma. We have previously demonstrated that sera from PDAC patients contain IgG autoantibodies to a-enolase. The present work was intended to assess the ability of a-enolase to induce antigen-specific T cell responses. We show that a-enolase-pulsed dendritic cells (DC) specifically stimulate healthy autologous T cells to proliferate, secrete IFN-c and lyse PDAC cells but not normal cells. In vivo, a-enolase-specific T cells inhibited the growth of PDAC cells in immunodeficient mice. In 8 out of 12 PDAC patients with circulating IgG to a-enolase, the existence of a-enolase-specific T cells was also demonstrated. Taken as a whole, these results indicate that a-enolase elicits a PDAC-specific, integrated humoral and cellular response. It is thus a promising and clinically relevant molecular target candidate for immunotherapeutic approaches as new adjuvants to conventional treatments in pancreatic cancer. ' 2009 UICC

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A Subset of Proteins Found in Culture Supernatants of Candida albicans Includes the Abundant, Immunodominant, Glycolytic Enzyme Enolase

Cited by 59 publications

References 14 publications

Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells

Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is a surface antigen

An integrated humoral and cellular response is elicited in pancreatic cancer by α‐enolase, a novel pancreatic ductal adenocarcinoma‐associated antigen

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