{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:11:35Z","timestamp":1788304295382,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012500","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000}}],"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2023-00208115"],"award-info":[{"award-number":["RS-2023-00208115"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI22C0177"],"award-info":[{"award-number":["HI22C0177"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003715","name":"Korea Research Institute of Bioscience and Biotechnology","doi-asserted-by":"publisher","award":["KGM4572431"],"award-info":[{"award-number":["KGM4572431"]}],"id":[{"id":"10.13039\/501100003715","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>NADPH oxidase 2 (NOX2) is an enzyme responsible for generating reactive oxygen species, primarily found in phagocytes. Chronic Granulomatous Disease (CGD), along with bacterial infections such as <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (Mtb), is a representative NOX2-deficient X-linked disease characterized by uncontrolled inflammation. However, the precise roles of host-derived factors that induce infection-mediated hyperinflammation in NOX2-deficient condition remain incompletely understood. To address this, we compared Mtb-induced pathogenesis in <jats:italic>Nox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> and wild type (WT) mice in a sex-dependent manner. Among age- and sex-matched mice subjected to Mtb infection, male <jats:italic>Nox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice exhibited a notable increase in bacterial burden and lung inflammation. This was characterized by significantly elevated pro-inflammatory cytokines such as G-CSF, TNF-\u03b1, IL-1\u03b1, IL-1\u03b2, and IL-6, excessive neutrophil infiltration, and reduced pulmonary lymphocyte levels as tuberculosis (TB) progressed. Notably, lungs of male <jats:italic>Nox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice were predominantly populated with CD11b<jats:sup>int<\/jats:sup>Ly6G<jats:sup>int<\/jats:sup>CXCR2<jats:sup>lo<\/jats:sup>CD62L<jats:sup>lo<\/jats:sup> immature neutrophils which featured mycobacterial permissiveness. By diminishing total lung neutrophils or reducing immature neutrophils, TB immunopathogenesis was notably abrogated in male <jats:italic>Nox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice. Ultimately, we identified G-CSF as the pivotal trigger that exacerbates the generation of immature permissive neutrophils, leading to TB immunopathogenesis in male <jats:italic>Nox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice. In contrast, neutralizing IL-1\u03b1 and IL-1\u03b2, which are previously known factors responsible for TB pathogenesis in <jats:italic>Nox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice, aggravated TB immunopathogenesis. Our study revealed that G-CSF-driven immature and permissive pulmonary neutrophils are the primary cause of TB immunopathogenesis and lung hyperinflammation in male <jats:italic>Nox2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice. This highlights the importance of quantitative and qualitative control of pulmonary neutrophils to alleviate TB progression in a phagocyte oxidase-deficient condition.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012500","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T18:23:48Z","timestamp":1724437428000},"page":"e1012500","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Permissive lung neutrophils facilitate tuberculosis immunopathogenesis in male phagocyte NADPH oxidase-deficient mice"],"prefix":"10.1371","volume":"20","author":[{"given":"Eunsol","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Hee","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kee Woong","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagyu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hwan","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Joo","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0854-4582","authenticated-orcid":true,"given":"Sung Jae","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ppat.1012500.ref001","volume-title":"Global Tuberculosis Report 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