{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:12:12Z","timestamp":1768907532040,"version":"3.49.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Mycobacterium abscessus<\/jats:italic> (<jats:italic>M. abscessus<\/jats:italic>) is a highly drug-resistant pathogen responsible for chronic pulmonary inflammation in humans. The cardiac glycoside ouabain exhibits broad anti-inflammatory effects in various disease models, but its therapeutic potential against <jats:italic>M. abscessus<\/jats:italic>-induced pneumonia remains unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the role of ouabain in <jats:italic>M. abscessus<\/jats:italic>-induced inflammation using <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>\u00a0models. Inflammatory responses were assessed through cytokine expression analysis (TNF-\u03b1, IL-6, IL-1\u03b2), histopathological examination (H&amp;amp;E staining), transcriptomic profiling, IHC, TEM and qPCR. The effects of ouabain on NLRP3 inflammasome activation and macrophage polarization were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ouabain significantly reduced <jats:italic>M. abscessus<\/jats:italic>-induced inflammation by suppressing proinflammatory cytokines (TNF-\u03b1, IL-6, IL-1\u03b2) and attenuating lung tissue damage. Transcriptomic and qPCR analyses confirmed that ouabain downregulated NLRP3 inflammasome activity and IL-1\u03b2 secretion <jats:italic>in vivo<\/jats:italic>. <jats:italic>In vitro<\/jats:italic> studies further demonstrated that ouabain inhibited NLRP3 inflammasome activation and M1 macrophage polarization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings indicate that ouabain mitigates <jats:italic>M. abscessus<\/jats:italic>-induced pulmonary inflammation through dual mechanisms: suppression of NLRP3 inflammasome activation and modulation of M1 macrophage polarization. This study highlights ouabain\u2019s potential as a therapeutic candidate for <jats:italic>M. abscessus<\/jats:italic> infections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1633882","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T05:29:23Z","timestamp":1755235763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage 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