Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.

In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availabili...

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Autores principales:	Britta Stadelmann, María C Merino, Lo Persson, Staffan G Svärd
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb4874d66c3a4853ac39cec987199856
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spelling	oai:doaj.org-article:cb4874d66c3a4853ac39cec9871998562021-11-18T07:04:56ZArginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.1932-620310.1371/journal.pone.0045325https://doaj.org/article/cb4874d66c3a4853ac39cec9871998562012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028934/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful and that citrulline especially should gain further attention in future treatment strategies.Britta StadelmannMaría C MerinoLo PerssonStaffan G SvärdPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45325 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Britta Stadelmann María C Merino Lo Persson Staffan G Svärd Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.
description	In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful and that citrulline especially should gain further attention in future treatment strategies.
format	article
author	Britta Stadelmann María C Merino Lo Persson Staffan G Svärd
author_facet	Britta Stadelmann María C Merino Lo Persson Staffan G Svärd
author_sort	Britta Stadelmann
title	Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.
title_short	Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.
title_full	Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.
title_fullStr	Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.
title_full_unstemmed	Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.
title_sort	arginine consumption by the intestinal parasite giardia intestinalis reduces proliferation of intestinal epithelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cb4874d66c3a4853ac39cec987199856
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Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.

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