Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection

Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino a...

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Main Authors:	Barry, Daniel P., Asim, Mohammad, Scull, Brooks P., Piazuelo, M. Blanca, de Sablet, Thibaut, Lewis, Nuruddeen D., Coburn, Lori A., Singh, Kshipra, Ellies, Lesley G., Gobert, Alain P., Chaturvedi, Rupesh, Wilson, Keith T.
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237590/

id	pubmed-3237590
recordtype	oai_dc
spelling	pubmed-32375902011-12-22 Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection Barry, Daniel P. Asim, Mohammad Scull, Brooks P. Piazuelo, M. Blanca de Sablet, Thibaut Lewis, Nuruddeen D. Coburn, Lori A. Singh, Kshipra Ellies, Lesley G. Gobert, Alain P. Chaturvedi, Rupesh Wilson, Keith T. Research Article Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino acid transporter 2 (CAT2) is essential for transport of l-arginine (L-Arg) into monocytic immune cells during H. pylori infection. Once within the cell, this amino acid is utilized by opposing pathways that lead to elaboration of either bactericidal nitric oxide (NO) produced from inducible NO synthase (iNOS), or hydrogen peroxide, which causes macrophage apoptosis, via arginase and the polyamine pathway. Because of its central role in controlling L-Arg availability in macrophages, we investigated the importance of CAT2 in vivo during H. pylori infection. CAT2−/− mice infected for 4 months exhibited decreased gastritis and increased levels of colonization compared to wild type mice. We observed suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor in CAT2−/− mice suggesting that CAT2 is involved in enhancing the innate immune response. In addition, cytokine expression in CAT2−/− mice was altered from an antimicrobial Th1 response to a Th2 response, indicating that the transporter has downstream effects on adaptive immunity as well. These findings demonstrate that CAT2 is an important regulator of the immune response during H. pylori infection. Public Library of Science 2011-12-14 /pmc/articles/PMC3237590/ /pubmed/22194986 http://dx.doi.org/10.1371/journal.pone.0029046 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Barry, Daniel P. Asim, Mohammad Scull, Brooks P. Piazuelo, M. Blanca de Sablet, Thibaut Lewis, Nuruddeen D. Coburn, Lori A. Singh, Kshipra Ellies, Lesley G. Gobert, Alain P. Chaturvedi, Rupesh Wilson, Keith T.
spellingShingle	Barry, Daniel P. Asim, Mohammad Scull, Brooks P. Piazuelo, M. Blanca de Sablet, Thibaut Lewis, Nuruddeen D. Coburn, Lori A. Singh, Kshipra Ellies, Lesley G. Gobert, Alain P. Chaturvedi, Rupesh Wilson, Keith T. Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection
author_facet	Barry, Daniel P. Asim, Mohammad Scull, Brooks P. Piazuelo, M. Blanca de Sablet, Thibaut Lewis, Nuruddeen D. Coburn, Lori A. Singh, Kshipra Ellies, Lesley G. Gobert, Alain P. Chaturvedi, Rupesh Wilson, Keith T.
author_sort	Barry, Daniel P.
title	Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection
title_short	Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection
title_full	Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection
title_fullStr	Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection
title_full_unstemmed	Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection
title_sort	cationic amino acid transporter 2 enhances innate immunity during helicobacter pylori infection
description	Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino acid transporter 2 (CAT2) is essential for transport of l-arginine (L-Arg) into monocytic immune cells during H. pylori infection. Once within the cell, this amino acid is utilized by opposing pathways that lead to elaboration of either bactericidal nitric oxide (NO) produced from inducible NO synthase (iNOS), or hydrogen peroxide, which causes macrophage apoptosis, via arginase and the polyamine pathway. Because of its central role in controlling L-Arg availability in macrophages, we investigated the importance of CAT2 in vivo during H. pylori infection. CAT2−/− mice infected for 4 months exhibited decreased gastritis and increased levels of colonization compared to wild type mice. We observed suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor in CAT2−/− mice suggesting that CAT2 is involved in enhancing the innate immune response. In addition, cytokine expression in CAT2−/− mice was altered from an antimicrobial Th1 response to a Th2 response, indicating that the transporter has downstream effects on adaptive immunity as well. These findings demonstrate that CAT2 is an important regulator of the immune response during H. pylori infection.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237590/
_version_	1611493982344314880

Cationic Amino Acid Transporter 2 Enhances Innate Immunity during Helicobacter pylori Infection

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