Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis.
The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is p...
Published in: | PLoS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:8b0ed627fc784c1794f8566af2bf7b7a 2023-05-15T15:05:59+02:00 Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. Manuel Modolell Beak-San Choi Robert O Ryan Maggie Hancock Richard G Titus Tamrat Abebe Asrat Hailu Ingrid Müller Matthew E Rogers Charles R M Bangham Markus Munder Pascale Kropf 2009-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000480 https://doaj.org/article/8b0ed627fc784c1794f8566af2bf7b7a EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2703824?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000480 https://doaj.org/article/8b0ed627fc784c1794f8566af2bf7b7a PLoS Neglected Tropical Diseases, Vol 3, Iss 7, p e480 (2009) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2009 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000480 2022-12-31T05:33:58Z The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-gamma, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 3 7 e480 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Manuel Modolell Beak-San Choi Robert O Ryan Maggie Hancock Richard G Titus Tamrat Abebe Asrat Hailu Ingrid Müller Matthew E Rogers Charles R M Bangham Markus Munder Pascale Kropf Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-gamma, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy. |
format |
Article in Journal/Newspaper |
author |
Manuel Modolell Beak-San Choi Robert O Ryan Maggie Hancock Richard G Titus Tamrat Abebe Asrat Hailu Ingrid Müller Matthew E Rogers Charles R M Bangham Markus Munder Pascale Kropf |
author_facet |
Manuel Modolell Beak-San Choi Robert O Ryan Maggie Hancock Richard G Titus Tamrat Abebe Asrat Hailu Ingrid Müller Matthew E Rogers Charles R M Bangham Markus Munder Pascale Kropf |
author_sort |
Manuel Modolell |
title |
Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. |
title_short |
Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. |
title_full |
Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. |
title_fullStr |
Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. |
title_full_unstemmed |
Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. |
title_sort |
local suppression of t cell responses by arginase-induced l-arginine depletion in nonhealing leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2009 |
url |
https://doi.org/10.1371/journal.pntd.0000480 https://doaj.org/article/8b0ed627fc784c1794f8566af2bf7b7a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 3, Iss 7, p e480 (2009) |
op_relation |
http://europepmc.org/articles/PMC2703824?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000480 https://doaj.org/article/8b0ed627fc784c1794f8566af2bf7b7a |
op_doi |
https://doi.org/10.1371/journal.pntd.0000480 |
container_title |
PLoS Neglected Tropical Diseases |
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3 |
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7 |
container_start_page |
e480 |
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