Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells
2008 (English)In: Molecular and biochemical parasitology (Print), ISSN 0166-6851, Vol. 159, no 2, 85-91 p.Article in journal (Refereed) Published
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.
Parasite, Cell–cell interaction, Innate immunity, Secretory product, Arginine deiminase, Enolase
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-16513DOI: 10.1016/j.molbiopara.2008.02.005ISI: 000256198000001PubMedID: 18359106OAI: oai:DiVA.org:uu-16513DiVA: diva2:44284