Arginase Activity - A Marker of Disease Status in Patients with Visceral Leishmaniasis in Ethiopia

被引:47
作者
Abebe, Tamrat [1 ,2 ]
Takele, Yegnasew [3 ]
Weldegebreal, Teklu [3 ]
Cloke, Tom [4 ]
Closs, Ellen [5 ]
Corset, Camille [4 ]
Hailu, Asrat [1 ]
Hailu, Workagegnehu [6 ]
Sisay, Yifru [6 ]
Corware, Karina [4 ]
Corset, Margaux [7 ]
Modolell, Manuel [8 ]
Munder, Markus [9 ]
Tacchini-Cottier, Fabienne [2 ]
Mueller, Ingrid [4 ]
Kropf, Pascale [7 ]
机构
[1] Univ Addis Ababa, Dept Microbiol Immunol & Parasitol, Addis Ababa, Ethiopia
[2] Univ Lausanne, Dept Biochem, WHO Immunol Res & Training Ctr, Lausanne, Switzerland
[3] Gondar Univ, Leishmaniasis Res & Treatment Ctr, Gondar, Ethiopia
[4] Univ London Imperial Coll Sci Technol & Med, Dept Med, Immunol Sect, London, England
[5] Johannes Gutenberg Univ Mainz, Inst Pharmacol, Univ Med Ctr, D-55122 Mainz, Germany
[6] Univ Gondar, Coll Med & Hlth Sci, Gondar, Ethiopia
[7] London Sch Hyg & Trop Med, Immunol & Infect Dept, London WC1, England
[8] Max Planck Inst Immunobiol & Epigenet, Dept Cellular Immunol, Freiburg, Germany
[9] Univ Med Ctr Mainz, Dept Med Hematol Oncol & Pneumol 3, Mainz, Germany
基金
英国惠康基金;
关键词
PLASMA AMINO-ACIDS; CYTOKINE PROFILES; SUPPRESSOR-CELLS; L-ARGININE; GRANULOCYTES; MECHANISMS; EXPRESSION; INFECTION; CANCER;
D O I
10.1371/journal.pntd.0002134
中图分类号
R51 [传染病];
学科分类号
100201 [内科学];
摘要
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 CD3 zeta in T cells.
引用
收藏
页数:10
相关论文
共 46 条
[1]
Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia [J].
Abebe, Tamrat ;
Hailu, Asrat ;
Woldeyes, Mihretu ;
Mekonen, Woinshet ;
Bilcha, Kassahun ;
Cloke, Thomas ;
Fry, Lionel ;
al Basatena, Nafisa-Katrin Seich ;
Corware, Karina ;
Modolell, Manuel ;
Munder, Markus ;
Tacchini-Cottier, Fabienne ;
Mueller, Ingrid ;
Kropf, Pascale .
PLOS NEGLECTED TROPICAL DISEASES, 2012, 6 (06)
[2]
[Anonymous], 2006, VISC LEISHM DIAGN TR
[3]
IL-27 and IL-21 Are Associated with T Cell IL-10 Responses in Human Visceral Leishmaniasis [J].
Ansari, Nasim Akhtar ;
Kumar, Rajiv ;
Gautam, Shalini ;
Nylen, Susanne ;
Singh, Om Prakash ;
Sundar, Shyam ;
Sacks, David .
JOURNAL OF IMMUNOLOGY, 2011, 186 (07) :3977-3985
[4]
Regulation of immune responses by L- arginine metabolism [J].
Bronte, V ;
Zanovello, P .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (08) :641-654
[5]
MONONUCLEAR CELL SUBPOPULATIONS AND CYTOKINE LEVELS IN HUMAN VISCERAL LEISHMANIASIS BEFORE AND AFTER CHEMOTHERAPY [J].
CENINI, P ;
BERHE, N ;
HAILU, A ;
MCGINNES, K ;
FROMMEL, D .
JOURNAL OF INFECTIOUS DISEASES, 1993, 168 (04) :986-993
[6]
IN-VIVO AND IN-VITRO CYTOKINE PROFILES AND MONONUCLEAR CELL SUBSETS IN SICILIAN PATIENTS WITH ACTIVE VISCERAL LEISHMANIASIS [J].
CILLARI, E ;
VITALE, G ;
ARCOLEO, F ;
DAGOSTINO, P ;
MOCCIARO, C ;
GAMBINO, G ;
MALTA, R ;
STASSI, G ;
GIORDANO, C ;
MILANO, S ;
MANSUETO, S .
CYTOKINE, 1995, 7 (07) :740-745
[7]
Cloke T, 2012, PLOS ONE IN PRESS
[8]
Cloke T, 2011, IMMUNOREGULATION ARG
[9]
Increased Level of Arginase Activity Correlates with Disease Severity in HIV-Seropositive Patients [J].
Cloke, T. E. ;
Garvey, L. ;
Choi, B. -S. ;
Abebe, T. ;
Hailu, A. ;
Hancock, M. ;
Kadolsky, U. ;
Bangham, C. R. M. ;
Munder, M. ;
Mueller, I. ;
Taylor, G. P. ;
Kropf, P. .
JOURNAL OF INFECTIOUS DISEASES, 2010, 202 (03) :374-385
[10]
Impairment of the extrusion transporter for asymmetric dimethyl-L-arginine: A novel mechanism underlying vasospastic angina [J].
Closs, Ellen I. ;
Ostad, Mir A. ;
Simon, Alexandra ;
Warnholtz, Ascan ;
Jabs, Alexander ;
Habermeier, Alice ;
Daiber, Andreas ;
Foerstermann, Ulrich ;
Muenzel, Thomas .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 423 (02) :218-223