Journal article
An effect of parasite-encoded arginase on the outcome of murine cutaneous leishmaniasis
The Journal of immunology (1950), Vol.179(12), pp.8446-8453
12/15/2007
DOI: 10.4049/jimmunol.179.12.8446
PMID: 18056391
Abstract
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 (Deltaarg), as well as wild-type and complemented Deltaarg controls (Deltaarg[pArg]), was implemented. The studies showed: 1) the absence of parasite arginase resulted in a significantly attenuated infection of mice (p<0.05); 2) poorer survival of Deltaarg in mouse macrophages than controls correlated with greater NO generation; 3) the difference between Deltaarg or control intracellular survival was abrogated in iNOS-deficient macrophages, suggesting iNOS activity was responsible for increased Deltaarg killing; 4) consistently, immunohistochemistry showed enhanced nitrotyrosine modifications in tissues of mice infected with Deltaarg compared with control parasites. Furthermore, 5) in the face of decreased parasite survival, lymph node cells draining cutaneous lesions of Deltaarg parasites produced more IFN-gamma 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.
Details
- Title: Subtitle
- An effect of parasite-encoded arginase on the outcome of murine cutaneous leishmaniasis
- Creators
- Upasna Gaur - Department of Internal Medicine, University of Iowa, and Veterans Affairs Medical Center, Iowa City 52242, USASigrid C RobertsRahul P DalviInés CorralizaBuddy UllmanMary E Wilson
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.179(12), pp.8446-8453
- Publisher
- United States
- DOI
- 10.4049/jimmunol.179.12.8446
- PMID
- 18056391
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- AI048822 / NIAID NIH HHS AI10096 / NIAID NIH HHS AI45540 / NIAID NIH HHS T32 AI07511 / NIAID NIH HHS AI067874 / NIAID NIH HHS AI41622 / NIAID NIH HHS
- Language
- English
- Date published
- 12/15/2007
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001158802771
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