L-arginine deprivation impairs Leishmania major-specific T-cell responses.


Munder, M; Choi, BS; Rogers, M; Kropf, P; (2009) L-arginine deprivation impairs Leishmania major-specific T-cell responses. European journal of immunology, 39 (8). pp. 2161-72. ISSN 0014-2980 DOI: https://doi.org/10.1002/eji.200839041

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Abstract

The amino acid L-arginine plays a crucial role in the regulation of immune responses. We have recently shown that uncontrolled replication of Leishmania parasites at the site of pathology correlates with high levels of arginase activity in nonhealing leishmaniasis and that this elevated arginase activity causes local depletion of L-arginine. To further our understanding of the impact of L-arginine deprivation in experimental leishmaniasis, here we characterize in detail the effects of L-arginine deprivation on antigen-specific T cells and MPhi. The results of our study show that decrease of L-arginine levels in the extracellular milieu affects the biological activities of Leishmania major-specific T cells, both at the level of the magnitude and the quality of their responses. L. major-specific CD4(+) T cells rendered hyporesponsive by L-arginine deprivation can be partially rescued by addition of exogenous L-arginine to produce IL-4 and IL-10, but not to produce IFN-gamma. Furthermore, our results show that L-arginine deprivation also greatly impacts parasite growth in activated macrophages. In summary, our results suggest that L-arginine levels affect both Th cell responses and parasite replication.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Leishmaniasis Group
PubMed ID: 19637195
Web of Science ID: 269396100029
URI: http://researchonline.lshtm.ac.uk/id/eprint/1640

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