Abstract
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.
Highlights
Leishmania are intracellular parasites that live and multiply within macrophages in the mammalian host
Our first attempt was to investigate whether resident peritoneal macrophages, which represent a significant proportion of the total peritoneal population, express ectonucleotidases on their surfaces
We found that CD39 and CD73 enzymes were abundantly present in macrophages ex vivo, but the characteristics of these molecules in in vitro were yet to be elucidated
Summary
Leishmania are intracellular parasites that live and multiply within macrophages in the mammalian host. In order to survive in these cells, Leishmania amastigotes must resist or inhibit their microbicidal mechanisms [1]. Cutaneous leishmaniasis associated with Leishmania amazonensis infection is severe in both humans and experimental models [2, 3]. It is characterized by uncontrolled parasite replication and profound host immunosuppression [4–7]. This parasite has been shown to alter the host cell defense mechanisms in several ways such as inhibition of antigen presentation and inhibition of reactive oxygen species (ROS) and nitric oxide (NO) production [8–10]. The underlying mechanisms involved in the manipulation of the macrophage activation, remain largely unclear
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