{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T06:34:08Z","timestamp":1769927648665,"version":"3.49.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":834,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,10,11]],"date-time":"2020-10-11T00:00:00Z","timestamp":1602374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,10,11]],"date-time":"2020-10-11T00:00:00Z","timestamp":1602374400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The enzyme IDO-1 is involved in the first stage of tryptophan catabolism and has been described in both microbicidal and tolerogenic microenvironments. Previous data from our group have shown that IDO-1 is differentially regulated in the distinctive clinical forms of leprosy. The present study aims to investigate the mechanisms associated with IDO-1 expression and activity in human monocyte-derived dendritic cells (mDCs) after stimulation with irradiated Mycobacterium leprae and its fractions. M. leprae and its fractions induced the expression and activity of IDO-1 in human mDCs. Among the stimuli studied, irradiated M. leprae and its membrane fraction (MLMA) induced the production of proinflammatory cytokines TNF and IL-6 whereas irradiated M. leprae and its cytosol fraction (MLSA) induced an increase in IL-10. We investigated if TLR2 activation was necessary for IDO-1 induction in mDCs. We observed that in cultures treated with a neutralizing anti-TLR2 antibody, there was a decrease in IDO-1 activity and expression induced by M. leprae and MLMA. The same effect was observed when we used a MyD88 inhibitor. Our data demonstrate that coculture of mDCs with autologous lymphocytes induced an increase in regulatory T (Treg) cell frequency in MLSA-stimulated cultures, showing that M. leprae constituents may play opposite roles that may possibly be related to the dubious effect of IDO-1 in the different clinical forms of disease. Our data show that M. leprae and its fractions are able to differentially modulate the activity and functionality of IDO-1 in mDCs by a pathway that involves TLR2, suggesting that this enzyme may play an important role in leprosy immunopathogenesis.<\/jats:p>","DOI":"10.1002\/jlb.4a0320-188r","type":"journal-article","created":{"date-parts":[[2020,10,11]],"date-time":"2020-10-11T12:03:50Z","timestamp":1602417830000},"page":"167-176","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<i>Mycobacterium leprae<\/i>induces a tolerogenic profile in monocyte-derived dendritic cells via TLR2 induction of IDO"],"prefix":"10.1093","volume":"110","author":[{"given":"J\u00e9ssica A P","family":"Oliveira","sequence":"first","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Gandini","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorgenilce S","family":"Sales","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9rgio K","family":"Fujimori","sequence":"additional","affiliation":[{"name":"Laboratory for Development and Analytical Validation, Oswaldo Cruz Foundation, Farmanguinhos , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayara G M","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Cascalho-Platt Laboratory, Department of Surgery, University of Michigan , Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valber S","family":"Frutuoso","sequence":"additional","affiliation":[{"name":"Immunopharmacology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milton O","family":"Moraes","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Euzenir N","family":"Sarno","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria C V","family":"Pessolani","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-4227","authenticated-orcid":false,"given":"Roberta O","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation , Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,11]]},"reference":[{"key":"2023032108503255900_","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1128\/CMR.19.2.338-381.2006","article-title":"The continuing challenges of leprosy","volume":"19","author":"Scollard","year":"2006","journal-title":"Clin Microbiol Rev"},{"key":"2023032108503255900_","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1002\/eji.201142198","article-title":"CD163 favors Mycobacterium leprae survival and persistence by promoting anti-inflammatory pathways in lepromatous macrophages","volume":"42","author":"Moura","year":"2012","journal-title":"Eur J Immunol"},{"key":"2023032108503255900_","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri1457","article-title":"IDO expression by dendritic cells: tolerance and tryptophan catabolism","volume":"4","author":"Mellor","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"2023032108503255900_","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3390\/vaccines3030703","article-title":"The role of Indoleamine 2, 3-dioxygenase in immune suppression and autoimmunity","volume":"3","author":"Mbongue","year":"2015","journal-title":"Vaccine"},{"key":"2023032108503255900_","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.2174\/092986711795656018","article-title":"Regulation of expression and function of IDO in human dendritic cells","volume":"18","author":"Heitger","year":"2011","journal-title":"Curr Med 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