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Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
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2008 (English)In: Molecular and biochemical parasitology (Print), ISSN 0166-6851, E-ISSN 1872-9428, Vol. 159, no 2, 85-91 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2008. Vol. 159, no 2, 85-91 p.
Keyword [en]
Parasite, Cell–cell interaction, Innate immunity, Secretory product, Arginine deiminase, Enolase
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-16513DOI: 10.1016/j.molbiopara.2008.02.005ISI: 000256198000001PubMedID: 18359106OAI: oai:DiVA.org:uu-16513DiVA: diva2:44284
Available from: 2008-05-27 Created: 2008-05-27 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Host-Pathogen Responses during Giardia infections
Open this publication in new window or tab >>Host-Pathogen Responses during Giardia infections
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Giardia lamblia is a eukaryotic parasite of the upper small intestine of humans and animals. The infecting trophozoite cells do not invade the epithelium lining of the intestine, but attach to the brush border surface in the intestinal lumen. The giardiasis disease in humans is highly variable. Prior to this study, the molecular mechanisms involved in establishment of infection or cause of disease were largely uncharacterized.

In this thesis, the molecular relationship between Giardia and the human host is described. The interaction of the parasite with human epithelial cells was investigated in vitro. Changes in the transcriptome and proteome of the parasite and the host cells, and changes in the micro-environment of the infection have been identified using microarray technology, and 1- and 2-Dimensional SDS-PAGE protein mapping together with mass spectrometry identification.

The first large-scale description of cellular activities within host epithelial cells during Giardia infection is included in this thesis (Paper I). We identified a unique activation of the host immune response and induction of apoptosis upon infection by Giardia. Four important virulence factors of the parasite, directly linked to the success of Giardia infection, were characterized and are presented in Papers II and III. The parasite was shown to have immune-modulating capacities, and to release proteins during host-interaction that facilitate the establishment of infection. Additional putative virulence factors were found among Giardia genes transcriptionally up-regulated during early infection (Paper IV).

In summary, this thesis provides important insights into the molecular mechanisms of the host-parasite interaction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 689
Keyword
Giardia, parasite infection, host-parasite releationship, immune activation, virulence factor, immune evasion
National Category
Biochemistry and Molecular Biology Microbiology
Research subject
Microbiology
Identifiers
urn:nbn:se:uu:diva-108980 (URN)978-91-554-7652-6 (ISBN)
Public defence
2009-12-12, B41, Biomedicinskt Centrum, Husargatan 3, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2009-11-19 Created: 2009-10-06 Last updated: 2009-11-19Bibliographically approved

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