{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:38:24Z","timestamp":1776854304518,"version":"3.51.2"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,12,27]],"date-time":"2009-12-27T00:00:00Z","timestamp":1261872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Buruli ulcer, caused by Mycobacterium ulcerans infections, is a necrotizing skin disease whose pathogenesis is associated with the exotoxin mycolactone. Despite the relevance of this emergent disease, little is known on the immune response against the pathogen. Following the recent demonstration of an intramacrophage growth phase for M. ulcerans, we investigated the biological relevance of IFN-\u03b3 and the antimycobacterial mechanisms activated by this cytokine in M. ulcerans-infected macrophages. Three M. ulcerans strains were tested: 5114 (mutant mycolactone-negative, avirulent strain); 94\u20131327 (intermediate virulence); and 98\u2013912 (high virulence). We show in this study that IFN-\u03b3 is expressed in mouse-infected tissues and that IFN-\u03b3\u2013deficient mice display increased susceptibility to infection with strains 5114 and, to a lesser extent, 94\u20131327, but not with the highly virulent strain. Accordingly, IFN-\u03b3\u2013activated cultured macrophages controlled the proliferation of the avirulent and the intermediate virulent strains. Addition of mycolactone purified from strain 98\u2013912 to cultures of IFN-\u03b3\u2013activated macrophages infected with the mycolactone-negative strain led to a dose-dependent inhibition of the IFN-\u03b3\u2013induced protective mechanisms, involving phagosome maturation\/acidification and increased NO production, therefore resulting in increased bacterial burdens. Our findings suggest that the protection mediated by IFN-\u03b3 in M. ulcerans-infected macrophages is impaired by the local buildup of mycolactone.<\/jats:p>","DOI":"10.4049\/jimmunol.0902717","type":"journal-article","created":{"date-parts":[[2009,12,12]],"date-time":"2009-12-12T03:12:15Z","timestamp":1260587535000},"page":"947-955","source":"Crossref","is-referenced-by-count":48,"title":["IFN-\u03b3\u2013Dependent Activation of Macrophages during Experimental Infections by <i>Mycobacterium ulcerans<\/i> Is Impaired by the Toxin Mycolactone"],"prefix":"10.1093","volume":"184","author":[{"given":"Eg\u00eddio","family":"Torrado","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences"}]},{"given":"Alexandra G","family":"Fraga","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences"}]},{"given":"Elsa","family":"Logarinho","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences"}]},{"given":"Teresa G","family":"Martins","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences"}]},{"given":"Jenny A","family":"Carmona","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences"}]},{"given":"Jos\u00e9 B","family":"Gama","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences"}]},{"given":"Maria A","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Chemistry Research Center, School of Sciences, University of Minho , Braga,","place":["Portugal"]}]},{"given":"Fernanda","family":"Proen\u00e7a","sequence":"additional","affiliation":[{"name":"Chemistry Research Center, School of Sciences, University of Minho , Braga,","place":["Portugal"]}]},{"given":"Antonio G","family":"Castro","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences"}]},{"given":"Jorge","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences"}]}],"member":"286","published-online":{"date-parts":[[2009,12,27]]},"reference":[{"key":"2025032710022392200_r1","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1371\/journal.pmed.0020108","article-title":"Buruli ulcer (M. ulcerans infection): new insights, new hope for disease control.","volume":"2","author":"Johnson","year":"2005","journal-title":"PLoS Med."},{"key":"2025032710022392200_r2","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/0035-9203(93)90272-R","article-title":"Epidemiology of Buruli ulcer in Amansie West district, Ghana.","volume":"87","author":"Amofah","year":"1993","journal-title":"Trans. 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