The Ecto-5${}^{\prime }$nucleotidase/CD73 Mediates Leishmania amazonensis Survival in Macrophages

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.

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“…Previous studies have demonstrated that CD73 is associated with bacterial escape, enhancing neutrophil recruitment during Mycobacterium tuberculosis infection (Dubois-Colas et al, 2014;Petit-Jentreau et al, 2015). CD73 is crucial for reducing tissue damage and controlling Toxoplasma gondii infection (Yilmaz et al, 2017), and it increases L. amazonensis survival via immunomodulatory effects activated by adenosine receptors (Basu et al, 2020;Bajracharya et al, 2022).…”