{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:28:29Z","timestamp":1782818909586,"version":"3.54.5"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/50026\/2020, UIDP\/50026\/2020, SFRH\/BD\/73544\/2010"],"award-info":[{"award-number":["UIDB\/50026\/2020, UIDP\/50026\/2020, SFRH\/BD\/73544\/2010"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI106725"],"award-info":[{"award-number":["R01 AI106725"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Disseminated infection with the high virulence strain of\n                    <jats:italic>Mycobacterium avium<\/jats:italic>\n                    25291 leads to progressive thymic atrophy. We previously showed that\n                    <jats:italic>M. avium<\/jats:italic>\n                    -induced thymic atrophy results from increased glucocorticoid levels that synergize with nitric oxide (NO) produced by interferon gamma (IFN\u03b3) activated macrophages. Where and how these mediators act is not understood. We hypothesized that IFN\u03b3 and NO promote thymic atrophy through their effects on bone marrow (BM) T cell precursors and T cell differentiation in the thymus. We show that\n                    <jats:italic>M. avium<\/jats:italic>\n                    infection cause a reduction in the percentage and number of common lymphoid progenitors (CLP). Additionally, BM precursors from infected mice show an overall impaired ability to reconstitute thymi of RAGKO mice, in part due to IFN\u03b3. Thymi from infected mice present an IFN\u03b3 and NO-driven inflammation. When transplanted under the kidney capsule of uninfected mice, thymi from infected mice are unable to sustain T cell differentiation. Finally, we observed increased thymocyte death\n                    <jats:italic>via<\/jats:italic>\n                    apoptosis after infection, independent of both IFN\u03b3 and iNOS; and a decrease on active caspase-3 positive thymocytes, which is not observed in the absence of iNOS expression. Together our data suggests that\n                    <jats:italic>M. avium<\/jats:italic>\n                    -induced thymic atrophy results from a combination of defects mediated by IFN\u03b3 and NO, including alterations in the BM T cell precursors, the thymic structure and the thymocyte differentiation.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.696415","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T01:42:49Z","timestamp":1639964569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["IFN\u03b3 and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact on Mycobacterium avium-Induced Thymic Atrophy"],"prefix":"10.3389","volume":"12","author":[{"given":"Palmira","family":"Barreira-Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Melo-Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Nobrega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Roque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia","family":"Serre-Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida","family":"Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Armada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"de 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