Papel da sinalização purinérgica na infecção por Leishmania braziliensis

Abstract

Leishmaniasis are infectious-parasitic diseases caused by protozoa of the genus Leishmania. The infection process causes the release of ATP by cells and tissues. Extracellular ATP can be converted into adenosine by the enzymes CD39 and CD73. Adenosine has anti-inflammatory effects by binding to P1 receptors, especially A2A and A2B receptors. This work evaluated the role of purinergic signaling in the human immune response to Leishmania braziliensis. Data obtained from transcriptome analyzes (GEO GSE55664) show that patients with localized cutaneous leishmaniasis (LCL; n = 21), caused by L. braziliensis, showed higher expression of CD39, CD73 and A2A receptor than healthy controls (n = 7). On the other hand, A2BR expression was lower in patients with LCL. In patients, we found positive correlations between the expression of A2AR and IL1B, IL6 and IL32, while the expression of A2BR is negatively correlated with the expression of the genes of these cytokines. Parasitism rates were evaluated in human THP-1 macrophages infected by Leishmania braziliensis-GFP, which also expressed higher levels of A2AR, in the presence and absence of selective A2AR antagonists, at 24 and 48 hours. There was no change in parasitism rates in macrophages and in the production of cytokines and ROS. However, when the enzyme adenosine deaminase (ADA) is inhibited, the A2AR antagonist significantly reduces infection rates. These data suggest that L. braziliensis infection alters the expression of enzymes and receptors involved in purinergic signaling, and these changes are important in modulating the immune response during LCL.