{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:21Z","timestamp":1785430461270,"version":"3.56.0"},"reference-count":105,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006507","name":"Oswaldo Cruz Foundation","doi-asserted-by":"crossref","award":["VPPCB-007-FIO-18-2-61"],"award-info":[{"award-number":["VPPCB-007-FIO-18-2-61"]}],"id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI141526-01A1"],"award-info":[{"award-number":["R01AI141526-01A1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R01AI141526-01A1"],"award-info":[{"award-number":["R01AI141526-01A1"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["432434\/2018-6"],"award-info":[{"award-number":["432434\/2018-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"award":["432434\/2018-6"],"award-info":[{"award-number":["432434\/2018-6"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"crossref","award":["E26\/111.493\/2013"],"award-info":[{"award-number":["E26\/111.493\/2013"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"award":["E26\/111.493\/2013"],"award-info":[{"award-number":["E26\/111.493\/2013"]}],"id":[{"id":"https:\/\/ror.org\/03kk0s825","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Leprosy is a chronic infection caused by Mycobacterium leprae that, in addition to Schwann cells, macrophages, and adipocytes, also infects human peripheral blood monocytes and subverts their metabolism in its favor. Infection is marked by cholesterol and fatty acid accumulation in lipid droplets (LDs), and a reduction in mitochondrial membrane potential (\u0394\u03c8m). Previous studies showed that M. leprae downregulates adenosine receptor A2A (A2AR) expression in Schwann cells, while activation reduces LD accumulation and bacterial viability. Since A2AR controls immunometabolic response, we investigated whether A2AR signaling restrains M. leprae-driven reprogramming in monocytes. Methods: Peripheral blood mononuclear cells from healthy donors were enriched for monocytes and infected with M. leprae in the presence or absence of adenosinergic modulators (5\u2032AMP, adenosine (ADO), A2AR agonist CGS21680, the antagonist ZM241385, or A2BR antagonist, MRS1754). We used flow cytometry, fluorescence microscopy, and RT-qPCR to evaluate purinergic components expression and bacillary viability. LDs and \u0394\u03c8m were measured by fluorescence microscopy, and extracellular levels of inosine (INO) and hypoxanthine (HPX) by LC-MS\/MS. Results: The results show that infection increased CD39, ADA, A2AR and A3R expression, decreased ENT1, A1R and A2BR, and raised extracellular INO and HPX. In addition, 5\u2032AMP, ADO and CGS21680 reversed infection-induced LD accumulation. CGS21680 also restored \u0394\u03c8m and decreased intracellular M. leprae viability. Conclusions: Our data suggest that M. leprae suppresses A2AR signaling to favor its survival in monocytes, indicating that the extracellular ADO\u2013A2AR pathway may be a potential target to limit early M. leprae infection.<\/jats:p>","DOI":"10.3390\/metabo16050304","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:01:18Z","timestamp":1777474878000},"page":"304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A2A Receptor Activation Restores Lipid and Mitochondrial Homeostasis, Limiting Mycobacterium leprae Persistence in Human Monocytes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0776-8149","authenticated-orcid":false,"given":"Antonio M. Rodrigues","family":"Pereira","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Plinio M. Freire dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thabatta L. S. A.","family":"Rosa","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-8312","authenticated-orcid":false,"given":"Chyntia","family":"D\u00edaz Acosta","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biotechnology, Health Sciences Research Institute (IICS), National University of Asunci\u00f3n, Asunci\u00f3n 111421, Paraguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina G. C.","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago 8580745, Chile"},{"name":"Gerosciense Center for Brain Health and Metabolism (GERO), Santiago 8580745, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa D.","family":"Gutierres","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabr\u00edcio M. R.","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Medical Sciences Faculty, Rio de Janeiro State University (FCM\/UERJ), Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5733-8294","authenticated-orcid":false,"given":"Leticia M. S.","family":"Lery","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5823-311X","authenticated-orcid":false,"given":"Rafael","family":"Garrett","sequence":"additional","affiliation":[{"name":"Metabolomics Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina A.","family":"Alves","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolomics Applied to Systems Medicine, Natural Products Research Institute, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 A.","family":"Dias","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2717-6597","authenticated-orcid":false,"given":"Flavio A.","family":"Lara","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0743-1009","authenticated-orcid":false,"given":"Luciana Silva","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Medical Sciences Faculty, Rio de Janeiro State University (FCM\/UERJ), Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-4227","authenticated-orcid":false,"given":"Roberta Olmo","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina V.","family":"Pessolani","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcia","family":"Berr\u00eado-Pinho","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Deps, P., and Collin, S.M. 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