Adenosine A2A receptor as a potential regulator of Mycobacterium leprae survival mechanisms: new insights into leprosy neural damage

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorFundação Oswaldo Cruz-
Autor(es): dc.contributorUniversidad Nacional de Asunción-
Autor(es): dc.contributorInstituto Lauro de Souza Lima-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade Federal do Rio de Janeiro (UFRJ)-
Autor(es): dc.contributorColorado State University-
Autor(es): dc.contributorUniversidade do Estado do Rio de Janeiro (UERJ)-
Autor(es): dc.creatordos Santos, Plinio Marcos Freire-
Autor(es): dc.creatorDíaz Acosta, Chyntia Carolina-
Autor(es): dc.creatorRosa, Thabatta Leal Silveira Andrezo-
Autor(es): dc.creatorIshiba, Michelle Harumi-
Autor(es): dc.creatorDias, André Alves-
Autor(es): dc.creatorPereira, Antonio Marcos Rodrigues-
Autor(es): dc.creatorGutierres, Luísa Domingos-
Autor(es): dc.creatorPereira, Melissa Pontes-
Autor(es): dc.creatorda Silva Rocha, Matheus-
Autor(es): dc.creatorRosa, Patrícia Sammarco-
Autor(es): dc.creatorBertoluci, Daniele F. F.-
Autor(es): dc.creatorMeyer-Fernandes, José Roberto-
Autor(es): dc.creatorda Mota Ramalho Costa, Fabricio-
Autor(es): dc.creatorMarques, Maria Angela M.-
Autor(es): dc.creatorBelisle, John T.-
Autor(es): dc.creatorPinheiro, Roberta Olmo-
Autor(es): dc.creatorRodrigues, Luciana Silva-
Autor(es): dc.creatorPessolani, Maria Cristina Vidal-
Autor(es): dc.creatorBerrêdo-Pinho, Marcia-
Data de aceite: dc.date.accessioned2025-08-21T22:47:55Z-
Data de disponibilização: dc.date.available2025-08-21T22:47:55Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3389/fphar.2024.1399363-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/301069-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/301069-
Descrição: dc.descriptionBackground: 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.-
Descrição: dc.descriptionLaboratório de Microbiologia Celular Instituto Oswaldo Cruz Fundação Oswaldo Cruz-
Descrição: dc.descriptionDepartamento de Biología Molecular y Biotecnología Instituto de Investigaciones en Ciencias de la Salud Universidad Nacional de Asunción-
Descrição: dc.descriptionDivisão de Pesquisa e Ensino Instituto Lauro de Souza Lima-
Descrição: dc.descriptionDepartamento de Doenças Tropicais Faculdade de Medicina de Botucatu Universidade Estadual Paulista-
Descrição: dc.descriptionLaboratório de Bioquímica Celular Instituto de Bioquímica Médica Leopoldo de Meis Centro de Ciências da Saúde Universidade Federal do Rio de Janeiro-
Descrição: dc.descriptionDepartment of Microbiology Immunology and Pathology Colorado State University-
Descrição: dc.descriptionLaboratório de Hanseníase Instituto Oswaldo Cruz Fundação Oswaldo Cruz-
Descrição: dc.descriptionLaboratório de Imunopatologia Faculdade de Ciências Médicas Universidade do Estado do Rio de Janeiro-
Descrição: dc.descriptionDepartamento de Doenças Tropicais Faculdade de Medicina de Botucatu Universidade Estadual Paulista-
Idioma: dc.languageen-
Relação: dc.relationFrontiers in Pharmacology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectA2A receptor-
Palavras-chave: dc.subjectadenosinergic system-
Palavras-chave: dc.subjectbacterial viability-
Palavras-chave: dc.subjectLeprosy-
Palavras-chave: dc.subjectlipid droplet-
Palavras-chave: dc.subjectM. leprae-
Palavras-chave: dc.subjectschwann cell-
Título: dc.titleAdenosine A2A receptor as a potential regulator of Mycobacterium leprae survival mechanisms: new insights into leprosy neural damage-
Tipo de arquivo: dc.typelivro digital-
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