Adenosine A receptor as a potential regulator of survival mechanisms: new insights into leprosy neural damage.

BACKGROUND

Leprosy is a chronic infectious disease caused by , which can lead to a disabling neurodegenerative condition. preferentially infects skin macrophages and Schwann cells-glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival. Although researchers have made progress in understanding leprosy pathogenesis, many aspects of the molecular and cellular mechanisms of host-pathogen interaction still require clarification. The purinergic system utilizes extracellular ATP and adenosine as critical signaling molecules and plays several roles in pathophysiological processes. Furthermore, nucleoside surface receptors such as the adenosine receptor AR involved in neuroimmune response, lipid metabolism, and neuron-glia interaction are targets for the treatment of different diseases. Despite the importance of this system, nothing has been described about its role in leprosy, particularly adenosinergic signaling (AdoS) during -Schwann cell interaction.

METHODS

was purified from the hind footpad of athymic mice. ST88-14 human cells were infected with in the presence or absence of specific agonists or antagonists of AdoS. Enzymatic activity assays, fluorescence microscopy, Western blotting, and RT-qPCR analysis were performed. viability was investigated by RT-qPCR, and cytokines were evaluated by enzyme-linked immunosorbent assay.

RESULTS

We demonstrated that -infected Schwann cells upregulated CD73 and ADA and downregulated AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of AR with its selective agonist, CGS21680, resulted in: 1) reduced lipid droplets accumulation and pro-lipogenic gene expression; 2) reduced production of IL-6 and IL-8; 3) reduced intracellular viability; 4) increased levels of p-CREB.

CONCLUSION

These findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that , by downmodulating the expression and activity of AR in Schwann cells, decreases AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus.