{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:18:36Z","timestamp":1760235516865,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Leprosy reactional episodes are acute inflammatory events that may occur during the clinical course of the disease. Type 1 reaction (T1R) is associated with an increase in neural damage, and the understanding of the molecular pathways related to T1R onset is pivotal for the development of strategies that may effectively control the reaction. Interferon-gamma (IFN-\u03b3) is a key cytokine associated with T1R onset and is also associated with autophagy induction. Here, we evaluated the modulation of the autophagy pathway in Mycobacterium leprae-stimulated cells in the presence or absence of IFN-\u03b3. We observed that IFN-\u03b3 treatment promoted autophagy activation and increased the expression of genes related to the formation of phagosomes, autophagy regulation and function, or lysosomal pathways in M. leprae-stimulated cells. IFN-\u03b3 increased interleukin (IL)-15 secretion in M. leprae-stimulated THP-1 cells in a process associated with autophagy activation. We also observed higher IL15 gene expression in multibacillary (MB) patients who later developed T1R during clinical follow-up when compared to MB patients who did not develop the episode. By overlapping gene expression patterns, we observed 13 common elements shared between T1R skin lesion cells and THP-1 cells stimulated with both M. leprae and IFN-\u03b3. Among these genes, the autophagy regulator Translocated Promoter Region, Nuclear Basket Protein (TPR) was significantly increased in T1R cells when compared with non-reactional MB cells. Overall, our results indicate that IFN-\u03b3 may induce a TPR-mediated autophagy transcriptional program in M. leprae-stimulated cells similar to that observed in skin cells during T1R by a pathway that involves IL-15 production, suggesting the involvement of this cytokine in the pathogenesis of T1R.<\/jats:p>","DOI":"10.3390\/cells10092215","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T09:53:23Z","timestamp":1630058003000},"page":"2215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Autophagy-Associated IL-15 Production Is Involved in the Pathogenesis of Leprosy Type 1 Reaction"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0362-1860","authenticated-orcid":false,"given":"Bruno Jorge de Andrade","family":"Silva","sequence":"first","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-6061","authenticated-orcid":false,"given":"Tamiris Lameira","family":"Bittencourt","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9520-4791","authenticated-orcid":false,"given":"Thyago","family":"Leal-Calvo","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayara Abud","family":"Mendes","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhana Berto da Silva","family":"Prata","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayara Garcia de Mattos","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscila Ribeiro","family":"Andrade","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzana","family":"C\u00f4rte-Real","sequence":"additional","affiliation":[{"name":"Structural Biology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilberto Marcelo","family":"Sperandio da Silva","sequence":"additional","affiliation":[{"name":"Evandro Chagas National Institute of Infectology, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milton Oz\u00f3rio","family":"Moraes","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Euzenir Nunes","family":"Sarno","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 21040-360, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.4269\/ajtmh.13-0221","article-title":"Risk factors for leprosy reactions in three endemic countries","volume":"92","author":"Scollard","year":"2015","journal-title":"Am. 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