The Ecto-5′nucleotidase/CD73 Mediates Leishmania amazonensis Survival in Macrophages

Endogenous nucleotides produced by various group of cells under inflammatory conditions act as potential danger signals in vivo. Extracellularly released nucleotides such as ATP are rapidly hydrolyzed to adenosine by the coordinated ectonucleotidase activities of CD39 and CD73. Leishmania is an obli...

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Detalhes bibliográficos
Autores: Bijay Bajracharya, Deena Shrestha, Andre Talvani Pedrosa da Silva, Ricardo Gonçalves, Luis Carlos Crocco Afonso
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Brasil
Recursos:Universidade Federal de Minas Gerais (UFMG)
Repositorio:Repositório Institucional da UFMG
Idioma:inglés
OAI Identifier:oai:repositorio.ufmg.br:1843/61018
Acesso em linha:https://doi.org/10.1155/2022/9928362
http://hdl.handle.net/1843/61018
https://orcid.org/0000-0003-2476-821X
https://orcid.org/0000-0003-1281-5330
https://orcid.org/0000-0002-6685-6229
https://orcid.org/0000-0002-1127-4483
https://orcid.org/0000-0003-2498-4086
Access Level:acceso abierto
Palavra-chave:Leishmania
Inflammation
Macrophages
Ectonucleotidases
Macrófagos
Inflamação
Descrição
Resumo:Endogenous nucleotides produced by various group of cells under inflammatory conditions act as potential danger signals in vivo. Extracellularly released nucleotides such as ATP are rapidly hydrolyzed to adenosine by the coordinated ectonucleotidase activities of CD39 and CD73. Leishmania is an obligate intracellular parasite of macrophages and capable of modulating host immune response in order to survive and multiply within host cells. In this study, the activity of CD73 induced by Leishmania amazonensis in infected macrophages has been investigated and correlated with parasite survival and infection in vitro. For this, the expression of CD39 and CD73, by flow cytometry, in murine peritoneal macrophages infected with metacyclic promastigotes of L. amazonensis has been analyzed. Our results showed that L. amazonensis-infected macrophages, unlike LPS-treated macrophages, increased CD73 expression. It was also noted that when CD73 enzymatic activity was blocked by α, β-methyleneadenosine 5-diphosphate sodium salt (APCP), macrophage parasitism was significantly decreased. Interestingly, these effects were not associated with the production of TNF-α, IL-10, or nitric oxide (NO). Together, these data demonstrate that L. amazonensis induces a regulatory phenotype in macrophages, which by activating the CD39/CD73 pathway allows parasite survival through the action of immunomodulatory adenosine receptors.