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Infection and Immunity, June 2007, p. 2802-2810, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.00026-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

L-Arginine and Cationic Amino Acid Transporter 2B Regulate Growth and Survival of Leishmania amazonensis Amastigotes in Macrophages

Nanchaya Wanasen,¹ Carol L. MacLeod,³ Lesley G. Ellies,³ and Lynn Soong^1,2*

Departments of Microbiology and Immunology,¹ Pathology, Institute for Human Infections and Immunity, Center for Biodefense and Emerging Infections, Sealy Center for Vaccine Development, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1070,² Cancer Center and Department of Medicine, University of California, San Diego, La Jolla, California 92093-0063³

Received 5 January 2007/ Returned for modification 20 February 2007/ Accepted 15 March 2007

Leishmania spp. are obligate intracellular parasites, requiring a suitable microenvironment for their growth within host cells. We previously reported that the growth of Leishmania amazonensis amastigotes in murine macrophages (Ms) was enhanced in the presence of gamma interferon (IFN-), a Th1 cytokine normally associated with classical M activation and killing of intracellular pathogens. In this study, we provided several lines of evidence suggesting that IFN--mediated parasite growth enhancement was associated with L-arginine transport via mouse cationic amino acid transporter 2B (mCAT-2B). (i) mRNA expression of Slc7A2, the gene encoding for mCAT-2B, as well as L-arginine transport was increased in IFN--treated Ms. (ii) Supplementation of L-arginine in M cultures increased parasite growth. (iii) Parasite growth enhancement in wild-type Ms was inhibited in the presence of nonmetabolized L-arginine analogues. (iv) IFN--mediated parasite growth was absent in Ms derived from mCAT-2B-deficient mice. Although we detected a clear upregulation of mCAT-2B and L-arginine transport, no measurable iNOS or arginase activities were observed in IFN--treated, infected Ms. Together, these data suggest an involvement of a novel L-arginine usage independent of iNOS and arginase activities during IFN--mediated parasite growth enhancement. A possible role of mCAT-2B in supplying L-arginine directly to the parasites for their proliferation is discussed.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Texas Medical Branch, Medical Research Building, Rm. 3.132, 301 University Blvd., Galveston, TX 77555-1070. Phone: (409) 772-8149. Fax: (409) 747-6869. E-mail: lysoong{at}utmb.edu

Published ahead of print on 26 March 2007.

Editor: W. A. Petri, Jr.

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Infection and Immunity, June 2007, p. 2802-2810, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.00026-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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