Arginase activity - a marker of disease status in patients with visceral leishmaniasis in Ethiopia
| Autor: | Markus Munder, Ellen I. Closs, Margaux Corset, Workagegnehu Hailu, Teklu Weldegebreal, Yifru Sisay, Camille Corset, Asrat Hailu, Manuel Modolell, Karina Corware, Yegnasew Takele, Pascale Kropf, Fabienne Tacchini-Cottier, Ingrid Müller, Tom Cloke, Tamrat Abebe |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
CUTANEOUS LEISHMANIASIS CD3 Complex Neutrophils medicine.medical_treatment T-Lymphocytes Biochemistry Antigens CD3 Immune tolerance 0302 clinical medicine INFECTION SUPPRESSOR-CELLS Immune Response PLASMA AMINO-ACIDS 0303 health sciences L-ARGININE T Cells lcsh:Public aspects of medicine PARASITOLOGY Immunosuppression 11 Medical And Health Sciences CANCER 3. Good health Arginase medicine.anatomical_structure Infectious Diseases Medicine Leishmaniasis Visceral Biological Markers Metabolic Pathways Life Sciences & Biomedicine Research Article EXPRESSION Adult lcsh:Arctic medicine. Tropical medicine Adolescent lcsh:RC955-962 T cell Immune Cells 030231 tropical medicine Immunology Biology Arginine Peripheral blood mononuclear cell Microbiology MECHANISMS Immunomodulation 03 medical and health sciences Young Adult Immune system Cutaneous leishmaniasis Tropical Medicine medicine Immune Tolerance ACTIVATED GRANULOCYTES Humans CYTOKINE PROFILES 030304 developmental biology Science & Technology Public Health Environmental and Occupational Health lcsh:RA1-1270 06 Biological Sciences medicine.disease Visceral leishmaniasis Metabolism Ethiopia Biomarkers |
| Zdroj: | PLoS Neglected Tropical Diseases, Vol 7, Iss 3, p e2134 (2013) PLoS Neglected Tropical Diseases, vol. 7, no. 3, pp. e2134 PLoS neglected tropical diseases PLoS Neglected Tropical Diseases |
| ISSN: | 1935-2727 |
| Popis: | The underlying mechanisms resulting in the profound immune suppression characteristic of human visceral leishmaniasis (VL) are not fully understood. Here, we tested the hypothesis that arginase, an enzyme associated with immunosuppression, is higher in patients with VL and contributes to impaired T cell responses. We recruited patients with VL before and after treatment and healthy controls and measured the arginase metabolism in the blood of these individuals. Our results show that arginase activity is significantly higher in the blood of patients with active VL as compared to controls. These high levels of arginase decline considerably once the patients are successfully treated. We identified the phenotype of arginase-expressing cells among PBMCs as neutrophils and show that their frequency was increased in PBMCs of patients before treatment; this coincides with reduced levels of L-arginine in the plasma and decreased expression levels of CD3ζ in T cells. Author Summary Leishmaniases, a group of diseases caused by a parasite, Leishmania, belong to the most neglected tropical diseases: they are mainly found in low-income countries and affect the poorest populations. These parasites infect cells of the immune system called macrophages, which can kill the intracellular parasites when they receive the right signals from other cells of the immune system, the lymphocytes. During the active phase of visceral leishmaniasis, it has been shown that lymphocytes lose their capacity to instruct the macrophages to kill the intracellular parasites. Here, we show that the levels of an enzyme, arginase, are significantly increased in the blood of patients with visceral leishmaniasis, but decrease to the same levels as those of healthy controls following successful treatment. Arginase has the capacity to deplete an amino acid, L-arginine, which is crucial for the activation of lymphocytes. Indeed, our results show that the levels of this amino acid are considerably decreased in patients with visceral leishmaniasis. Our results suggest that during the active phase of visceral leishmaniasis, increased arginase results in the depletion of L-arginine, which is responsible for the incapacity of lymphocytes to send the adequate signals to the macrophages. |
| Databáze: | OpenAIRE |
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