title: E-NTPDase (ecto-nucleoside triphosphate diphosphohydrolase) of Leishmania amazonensis inhibits macrophage activation.
abstract: Leishmania amazonensis, the causal agent of diffuse cutaneous leishmaniasis, is known for its ability to modulate the host immune response. Because a relationship between ectonucleotidase activity and the ability of Leishmania to generate injury in C57BL/6 mice has been demonstrated, in this study we evaluated the involvement of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity of L. amazonensis in the process of infection of J774-macrophages. Our results show that high-activity parasites show increased survival rate in LPS/IFN-γ-activated cells, by inhibiting the host-cell NO production. Conversely, inhibition of E-NTPDase activity reduces the parasite survival rates, an effect associated with increased macrophage NO production. E-NTPDase activity generates substrate for the production of extracellular adenosine, which binds to A2B receptors and reduces IL-12 and TNF-α produced by activated macrophages, thus inhibiting NO production. These results indicate that E-NTPDase activity is important for survival of L. amazonensis within macrophages, showing the role of the enzyme in modulating macrophage response and lower NO production, which ultimately favors infection. Our results point to a new mechanism of L. amazonensis infection that may pave the way for the development of new treatments for this neglected disease.
authors.affiliation: Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas/NUPEB, Universidade Federal de Ouro Preto, Campus do Morro do Cruzeiro, 35400-000 Ouro Preto, MG, Brazil.
authors.forename: Rodrigo Saar
authors.initials: RS
authors.lastname: Gomes
authors.affiliation: Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas/NUPEB, Universidade Federal de Ouro Preto, Campus do Morro do Cruzeiro, 35400-000 Ouro Preto, MG, Brazil.
authors.forename: Luana Cristina Faria
authors.initials: LC
authors.lastname: de Carvalho
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Laboratório de Infectologia Molecular Animal, Instituto de Biotecnologia Aplicada à Agropecuária/BIOAGRO, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil.
authors.forename: Raphael
authors.initials: R
authors.lastname: de Souza Vasconcellos
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Laboratório de Infectologia Molecular Animal, Instituto de Biotecnologia Aplicada à Agropecuária/BIOAGRO, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil.
authors.forename: Juliana Lopes Rangel
authors.initials: JL
authors.lastname: Fietto
authors.affiliation: Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas/NUPEB, Universidade Federal de Ouro Preto, Campus do Morro do Cruzeiro, 35400-000 Ouro Preto, MG, Brazil. Electronic address: afonso@nupeb.ufop.br.
authors.forename: Luís Carlos Crocco
authors.initials: LC
authors.lastname: Afonso
mesh_terms: D000251:Adenosine Triphosphatases / Q000009:adverse effects / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D007896:Leishmaniasis / Q000201:enzymology* / Q000276:immunology / Q000469:parasitology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000251:Adenosine Triphosphatases; C027201:ectoATPase
keywords: Adenosine; Cytokines; E-NTPDase; Leishmania amazonensis; Nitric oxide