{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:09:09Z","timestamp":1771466949790,"version":"3.50.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2007,12,1]],"date-time":"2007-12-01T00:00:00Z","timestamp":1196467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Classical activation of macrophages infected with Leishmania species results in expression and activation of inducible NO synthase (iNOS) leading to intracellular parasite killing. Macrophages can contrastingly undergo alternative activation with increased arginase activity, metabolism of arginine along the polyamine pathway, and consequent parasite survival. An active role for parasite-encoded arginase in host microbicidal responses has not previously been documented. To test the hypothesis that parasite-encoded arginase can influence macrophage responses to intracellular Leishmania, a comparative genetic approach featuring arginase-deficient mutants of L. mexicana lacking both alleles of the gene encoding arginase (\u0394arg), as well as wild-type and complemented \u0394arg controls (\u0394arg[pArg]), was implemented. The studies showed: 1) the absence of parasite arginase resulted in a significantly attenuated infection of mice (p &amp;lt; 0.05); 2) poorer survival of \u0394arg in mouse macrophages than controls correlated with greater NO generation; 3) the difference between \u0394arg or control intracellular survival was abrogated in iNOS-deficient macrophages, suggesting iNOS activity was responsible for increased \u0394arg killing; 4) consistently, immunohistochemistry showed enhanced nitrotyrosine modifications in tissues of mice infected with \u0394arg compared with control parasites. Furthermore, 5) in the face of decreased parasite survival, lymph node cells draining cutaneous lesions of \u0394arg parasites produced more IFN-\u03b3 and less IL-4 and IL-10 than controls. These data intimate that parasite-encoded arginase of Leishmania mexicana subverts macrophage microbicidal activity by diverting arginine away from iNOS.<\/jats:p>","DOI":"10.4049\/jimmunol.179.12.8446","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:25:48Z","timestamp":1397849148000},"page":"8446-8453","source":"Crossref","is-referenced-by-count":92,"title":["An Effect of Parasite-Encoded Arginase on the Outcome of Murine Cutaneous Leishmaniasis"],"prefix":"10.1093","volume":"179","author":[{"given":"Upasna","family":"Gaur","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Biochemistry, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigrid C","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul P","family":"Dalvi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ine\u0301s","family":"Corraliza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Universidad de Extremadura , Ca\u0301ceres ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Buddy","family":"Ullman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oregon Health and Science University , Portland, OR 97239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary E","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Epidemiology, University of Iowa , Iowa City, IA 52242"},{"name":"Veterans Affairs Medical Center , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,12,15]]},"reference":[{"key":"2026012809265675200_R1","first-page":"845","volume-title":"Nat. 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