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Using the mouse model of Mycobacterium avium infection, we show in this study that the production of NO from IFN-\u03b3\u2013activated macrophages plays a major role in mycobacterial infection-induced thymic atrophy. Our results show that disseminated infection with a highly virulent strain of M. avium, but not with a low-virulence strain, led to a progressive thymic atrophy. Thymic involution was prevented in genetically manipulated mice unable to produce IFN-\u03b3 or the inducible NO synthase. In addition, mice with a selective impairment of IFN-\u03b3 signaling in macrophages were similarly protected from infection-induced thymic atrophy. A slight increase in the concentration of corticosterone was found in mice infected with the highly virulent strain, and thymocytes presented an increased susceptibility to dexamethasone-induced death during disseminated infection. The administration of an antagonist of glucocorticoid receptors partially reverted the infection-induced thymic atrophy. We observed a reduction in all thymocyte populations analyzed, including the earliest thymic precursors, suggesting a defect during thymic colonization by T cell precursors and\/or during the differentiation of these cells in the bone marrow in addition to local demise of thymic cells. Our data suggest a complex picture underlying thymic atrophy during infection by M. avium with the participation of locally produced NO, endogenous corticosteroid activity, and reduced bone marrow seeding.<\/jats:p>","DOI":"10.4049\/jimmunol.1201525","type":"journal-article","created":{"date-parts":[[2012,8,25]],"date-time":"2012-08-25T04:05:56Z","timestamp":1345867556000},"page":"3600-3608","source":"Crossref","is-referenced-by-count":32,"title":["Molecular and Cellular Mechanisms of <i>Mycobacterium avium<\/i>-Induced Thymic Atrophy"],"prefix":"10.1093","volume":"189","author":[{"given":"Margarida","family":"Borges","sequence":"first","affiliation":[{"name":"Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]},{"name":"Department of Biological Sciences, Faculty of Pharmacy, University of Porto , 4050-313 Porto,","place":["Portugal"]}]},{"given":"Palmira","family":"Barreira-Silva","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences, University of Minho , 4710-057 Braga,","place":["Portugal"]},{"name":"Instituto de Investiga\u00e7\u00e3o em Ci\u00eancias da Vida e Sa\u00fade\/Biomateriais, Materiais Biodegrad\u00e1veis e Biomim\u00e9ticos, Portuguese Government Associate Laboratory , 4710-057 Braga\/Guimar\u00e3es,","place":["Portugal"]}]},{"given":"Manuela","family":"Fl\u00f3rido","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]}]},{"given":"Michael B","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"},{"name":"University of Cincinnati College of Medicine , Cincinnati, OH 45229"}]},{"given":"Margarida","family":"Correia-Neves","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences, University of Minho , 4710-057 Braga,","place":["Portugal"]}]},{"given":"Rui","family":"Appelberg","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2012,10,1]]},"reference":[{"key":"2025032409271629600_r1","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1371\/journal.ppat.0020062","article-title":"The thymus is a common target organ in infectious diseases","volume":"2","author":"Savino","year":"2006","journal-title":"PLoS Pathog."},{"key":"2025032409271629600_r2","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.it.2009.04.003","article-title":"Thymic involution and immune reconstitution","volume":"30","author":"Lynch","year":"2009","journal-title":"Trends Immunol."},{"key":"2025032409271629600_r3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/00002030-200002180-00007","article-title":"Early immune reconstitution after potent antiretroviral therapy in HIV-infected children correlates with the increase in thymus volume","volume":"14","author":"Vigano","year":"2000","journal-title":"AIDS"},{"key":"2025032409271629600_r4","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1086\/466527","article-title":"Distinct mechanisms of T cell reconstitution can be identified by estimating thymic volume in adult HIV-1 disease","volume":"192","author":"Kalayjian","year":"2005","journal-title":"J. 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