Age-related alteration of arginase activity impacts on severity of leishmaniasis.
The leishmaniases are a group of vector-borne parasitic diseases that represent a major international public health problem; they belong to the most neglected tropical diseases and have one of the highest rates of morbidity and mortality. The clinical outcome of infection with Leishmania parasites d...
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ftdoajarticles:oai:doaj.org/article:f0ce181d25fa4e02bc8e944b83704ec5 2023-05-15T15:14:21+02:00 Age-related alteration of arginase activity impacts on severity of leishmaniasis. Ingrid Müller Asrat Hailu Beak-San Choi Tamrat Abebe Jose M Fuentes Markus Munder Manuel Modolell Pascale Kropf 2008-05-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000235 https://doaj.org/article/f0ce181d25fa4e02bc8e944b83704ec5 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2359854?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000235 https://doaj.org/article/f0ce181d25fa4e02bc8e944b83704ec5 PLoS Neglected Tropical Diseases, Vol 2, Iss 5, p e235 (2008) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2008 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000235 2022-12-31T01:33:07Z The leishmaniases are a group of vector-borne parasitic diseases that represent a major international public health problem; they belong to the most neglected tropical diseases and have one of the highest rates of morbidity and mortality. The clinical outcome of infection with Leishmania parasites depends on a variety of factors such as parasite species, vector-derived products, genetics, behaviour, and nutrition. The age of the infected individuals also appears to be critical, as a significant proportion of clinical cases occur in children; this age-related higher prevalence of disease is most remarkable in visceral leishmaniasis. The mechanisms resulting in this higher incidence of clinical disease in children are poorly understood. We have recently revealed that sustained arginase activity promotes uncontrolled parasite growth and pathology in vivo. Here, we tested the hypothesis that arginase-mediated L-arginine metabolism differs with age.The age distribution of patients with visceral or cutaneous leishmaniasis was determined in cohorts of patients in our clinics in endemic areas in Ethiopia. To exclude factors that are difficult to control in patients, we assessed the impact of ageing on the manifestations of experimental leishmaniasis. We determined parasite burden, T cell responses, and macrophage effector functions in young and aged mice during the course of infection.Our results show that younger mice develop exacerbated lesion pathology and higher parasite burdens than aged mice. This aggravated disease development in younger individuals does not correlate with a change in T helper cytokine profile. To address the underlying mechanisms responsible for the more severe infections in younger mice, we investigated macrophage effector functions. Our results show that macrophages from younger mice do not have an impaired capacity to kill parasites; however, they express significantly higher levels of arginase 1 than aged mice and promote parasite growth more efficiently. Thus, our results demonstrate that ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 2 5 e235 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ingrid Müller Asrat Hailu Beak-San Choi Tamrat Abebe Jose M Fuentes Markus Munder Manuel Modolell Pascale Kropf Age-related alteration of arginase activity impacts on severity of leishmaniasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The leishmaniases are a group of vector-borne parasitic diseases that represent a major international public health problem; they belong to the most neglected tropical diseases and have one of the highest rates of morbidity and mortality. The clinical outcome of infection with Leishmania parasites depends on a variety of factors such as parasite species, vector-derived products, genetics, behaviour, and nutrition. The age of the infected individuals also appears to be critical, as a significant proportion of clinical cases occur in children; this age-related higher prevalence of disease is most remarkable in visceral leishmaniasis. The mechanisms resulting in this higher incidence of clinical disease in children are poorly understood. We have recently revealed that sustained arginase activity promotes uncontrolled parasite growth and pathology in vivo. Here, we tested the hypothesis that arginase-mediated L-arginine metabolism differs with age.The age distribution of patients with visceral or cutaneous leishmaniasis was determined in cohorts of patients in our clinics in endemic areas in Ethiopia. To exclude factors that are difficult to control in patients, we assessed the impact of ageing on the manifestations of experimental leishmaniasis. We determined parasite burden, T cell responses, and macrophage effector functions in young and aged mice during the course of infection.Our results show that younger mice develop exacerbated lesion pathology and higher parasite burdens than aged mice. This aggravated disease development in younger individuals does not correlate with a change in T helper cytokine profile. To address the underlying mechanisms responsible for the more severe infections in younger mice, we investigated macrophage effector functions. Our results show that macrophages from younger mice do not have an impaired capacity to kill parasites; however, they express significantly higher levels of arginase 1 than aged mice and promote parasite growth more efficiently. Thus, our results demonstrate that ... |
format |
Article in Journal/Newspaper |
author |
Ingrid Müller Asrat Hailu Beak-San Choi Tamrat Abebe Jose M Fuentes Markus Munder Manuel Modolell Pascale Kropf |
author_facet |
Ingrid Müller Asrat Hailu Beak-San Choi Tamrat Abebe Jose M Fuentes Markus Munder Manuel Modolell Pascale Kropf |
author_sort |
Ingrid Müller |
title |
Age-related alteration of arginase activity impacts on severity of leishmaniasis. |
title_short |
Age-related alteration of arginase activity impacts on severity of leishmaniasis. |
title_full |
Age-related alteration of arginase activity impacts on severity of leishmaniasis. |
title_fullStr |
Age-related alteration of arginase activity impacts on severity of leishmaniasis. |
title_full_unstemmed |
Age-related alteration of arginase activity impacts on severity of leishmaniasis. |
title_sort |
age-related alteration of arginase activity impacts on severity of leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2008 |
url |
https://doi.org/10.1371/journal.pntd.0000235 https://doaj.org/article/f0ce181d25fa4e02bc8e944b83704ec5 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 2, Iss 5, p e235 (2008) |
op_relation |
http://europepmc.org/articles/PMC2359854?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000235 https://doaj.org/article/f0ce181d25fa4e02bc8e944b83704ec5 |
op_doi |
https://doi.org/10.1371/journal.pntd.0000235 |
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PLoS Neglected Tropical Diseases |
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e235 |
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