The role of arginine and arginine-metabolizing enzymes during Giardia - host cell interactions in vitro.

Lundström-Stadelmann, Britta; Hanevik, Kurt; Andersson, Mattias K; Bruserud, Oystein; Svärd, Staffan G (2013). The role of arginine and arginine-metabolizing enzymes during Giardia - host cell interactions in vitro. BMC microbiology, 13(256), p. 256. BioMed Central 10.1186/1471-2180-13-256

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BACKGROUND Arginine is a conditionally essential amino acid important in growing individuals and under non-homeostatic conditions/disease. Many pathogens interfere with arginine-utilization in host cells, especially nitric oxide (NO) production, by changing the expression of host enzymes involved in arginine metabolism. Here we used human intestinal epithelial cells (IEC) and three different isolates of the protozoan parasite Giardia intestinalis to investigate the role of arginine and arginine-metabolizing enzymes during intestinal protozoan infections. RESULTS RNA expression analyses of major arginine-metabolizing enzymes revealed the arginine-utilizing pathways in human IECs (differentiated Caco-2 cells) grown in vitro. Most genes were constant or down-regulated (e.g. arginase 1 and 2) upon interaction with Giardia, whereas inducible NO synthase (iNOS) and ornithine decarboxylase (ODC) were up-regulated within 6 h of infection. Giardia was shown to suppress cytokine-induced iNOS expression, thus the parasite has both iNOS inducing and suppressive activities. Giardial arginine consumption suppresses NO production and the NO-degrading parasite protein flavohemoglobin is up-regulated in response to host NO. In addition, the secreted, arginine-consuming giardial enzyme arginine deiminase (GiADI) actively reduces T-cell proliferation in vitro. Interestingly, the effects on NO production and T cell proliferation could be reversed by addition of external arginine or citrulline. CONCLUSIONS Giardia affects the host's arginine metabolism on many different levels. Many of the effects can be reversed by addition of arginine or citrulline, which could be a beneficial supplement in oral rehydration therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Lundström Stadelmann, Britta

Subjects:

600 Technology > 630 Agriculture

ISSN:

1471-2180

Publisher:

BioMed Central

Language:

English

Submitter:

Monika Mumenthaler

Date Deposited:

21 Aug 2018 11:53

Last Modified:

15 Jan 2019 09:13

Publisher DOI:

10.1186/1471-2180-13-256

PubMed ID:

24228819

BORIS DOI:

10.7892/boris.119385

URI:

https://boris.unibe.ch/id/eprint/119385

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