title: Cationic amino acid transporter 2 enhances innate immunity during Helicobacter pylori infection.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Barry
authors.forename: Mohammad
authors.initials: M
authors.lastname: Asim
authors.forename: Brooks P
authors.initials: BP
authors.lastname: Scull
authors.forename: M Blanca
authors.initials: MB
authors.lastname: Piazuelo
authors.forename: Thibaut
authors.initials: T
authors.lastname: de Sablet
authors.forename: Nuruddeen D
authors.initials: ND
authors.lastname: Lewis
authors.forename: Lori A
authors.initials: LA
authors.lastname: Coburn
authors.forename: Kshipra
authors.initials: K
authors.lastname: Singh
authors.forename: Lesley G
authors.initials: LG
authors.lastname: Ellies
authors.forename: Alain P
authors.initials: AP
authors.lastname: Gobert
authors.forename: Rupesh
authors.initials: R
authors.lastname: Chaturvedi
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
mesh_terms: D000208:Acute Disease; D026923:Amino Acid Transport Systems, Basic / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D002908:Chronic Disease; D015169:Colony Count, Microbial; D003713:Dendritic Cells / Q000473:pathology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D026923:Amino Acid Transport Systems, Basic; C087435:Slc7a2 protein, mouse; D018664:Interleukin-12; D052247:Nitric Oxide Synthase Type II