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Dominant arginase expression in a model of progressive visceral leishmaniasis
Author(s) -
Osorio Yaneth E.,
Zhao Weiguo,
Espitia Claudia,
Travi Bruno L.,
Hawel Leo,
Byus Craig V.,
Saldarriaga Omar A.,
Melby Peter C.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.860.20
Subject(s) - arginase , hamster , leishmania , spleen , leishmania donovani , visceral leishmaniasis , downregulation and upregulation , macrophage , biology , polyamine , immunology , in vitro , microbiology and biotechnology , leishmaniasis , chemistry , biochemistry , parasite hosting , arginine , gene , amino acid , world wide web , computer science
Progressive disease in the hamster model of visceral leishmaniasis (VL), caused by Leishmania donovani, mimics human VL. During progressive infection in hamsters, there is low expression of NOS2 but high splenic arginase I mRNA expression (p=0.005) and enzyme activity (p=0.016), and its downstream products, polyamines (p<0.008). In contrast, the controlled infection in mice is accompanied by high NOS2 expression but low arginase activity and low polyamine production. Increased arginase activity and polyamine synthesis was also evident in an in vitro model of infected hamster macrophages (p<0.03). Leishmania arginase made little contribution to the overall increase in arginase activity. During progressive disease, there was increased STAT6‐inducing activity in the serum and spleen, and increased splenic expression of IL‐4, IL‐10, IL‐13, and IL‐21. Parasite‐induced macrophage arginase expression was amplified by exogenous IL‐4 and IL‐10, possibly through the infection‐induced upregulation of IL‐4 and IL‐10 receptors. The targeting of this pathway has therapeutic potential for this and other intracellular pathogens. Supported by NIAID.