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Transcriptional changes in Giardia during host-parasite interactions
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. (Prof. Staffan Svärd)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
2011 (English)In: International Journal for Parasitology, ISSN 0020-7519, Vol. 41, no 3-4, 277-285 p.Article in journal (Refereed) Published
Abstract [en]

Giardia intestinalis is one of the major causes of parasite-induced diarrhea. The disease, giardiasis, is caused by trophozoites attaching to the intestinal epithelium, resulting in apoptosis of intestinal epithelial cells, disrupted epithelial barrier function and malabsorption. Microarray studies have detected gene expression changes in intestinal epithelial cells (IECs), during interaction with Giardia trophozoites in vitro. In the present study we examined this host-parasite interaction further by transcriptional profiling of interacting trophozoites using Giardia oligo microarrays. A total of 325 Giardia transcripts were significantly changed during the interaction, lasting 1.5 to 18 hrs in complete DMEM medium. Quantitative real-time reverse transcriptase PCR confirmed these changes in all 12 genes tested using mRNA isolated in a separate experiment. Genes involved in cell division and attachment were down-regulated in the late time-points of interaction. Proteins earlier suggested to be important during host parasite interactions like arginine deiminase and cysteine proteinases changed their expression. Oxygen defense proteins and several members of the high cysteine-rich membrane protein (HCMp) family were up-regulated during the interaction with IECs. Thus, there are extensive gene-expression changes in Giardia trophozoites and IECs during host-parasite interactions and this can be important for establishment of infection and in the induction of giardiasis.

Place, publisher, year, edition, pages
2011. Vol. 41, no 3-4, 277-285 p.
Keyword [en]
Protozoa, intestinal epithelial cell, diarrhea, microarray
National Category
Biochemistry and Molecular Biology Infectious Medicine
Research subject
Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-109887DOI: 10.1016/j.ijpara.2010.09.011ISI: 000288736700002OAI: oai:DiVA.org:uu-109887DiVA: diva2:274443
Available from: 2009-10-29 Created: 2009-10-29 Last updated: 2011-04-15Bibliographically 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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