Please use this identifier to cite or link to this item:
Type
ArticleCopyright
Open access
Collections
- IOC - Artigos de Periódicos [12980]
Metadata
Show full item record
ADENOSINE A2A RECEPTOR AS A POTENTIAL REGULATOR OF MYCOBACTERIUM LEPRAE SURVIVAL MECHANISMS: NEW INSIGHTS INTO LEPROSY NEURAL DAMAGE
Schwann cell
M. leprae
Adenosinergic system
A2A receptor
Lipid droplet
Bacterial viability
Produção científica do Laboratório de Microbiologia Celular.
Author
Affilliation
Abstract
Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to a disabling neurodegenerative condition. M. leprae 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 A2AR 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 M. leprae–Schwann cell interaction. Methods: M. leprae was purified from the hind footpad of athymic nu/nu mice. ST88-14 human cells were infected with M. leprae 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. M. leprae viability was investigated by RT-qPCR, and cytokines were evaluated by enzyme-linked immunosorbent assay. Results: We demonstrated that M. leprae-infected Schwann cells upregulated CD73 and ADA and downregulated A2AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of A2AR 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 M. leprae viability; 4) increased levels of p-CREB. Conclusion: These findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that M. leprae, by downmodulating the expression and activity of A2AR in Schwann cells, decreases A2AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus.
Keywords
LeprosySchwann cell
M. leprae
Adenosinergic system
A2A receptor
Lipid droplet
Bacterial viability
Publisher
Frontiers Media
Citation
SANTOS, Plinio Marcos Freire dos et al. Adenosine A2A receptor as a potential regulator of Mycobacterium leprae survival mechanisms: new insights into leprosy neural damage. Frontiers in Pharmacology, v. 15, p. 1-19, 28 June 2024.DOI
10.3389/fphar.2024.1399363ISSN
1663-9812Notes
Produção científica do Laboratório de Hanseníase.Produção científica do Laboratório de Microbiologia Celular.
Share