{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:59:24Z","timestamp":1793048364553,"version":"4.5.0"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            NADPH oxidase is a crucial enzyme in antimicrobial host defense and in regulating inflammation. Chronic granulomatous disease (CGD) is an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates.\n            <jats:named-content content-type=\"genus-species\">Aspergillus<\/jats:named-content>\n            species are ubiquitous, filamentous fungi, which can cause invasive aspergillosis, a major cause of morbidity and mortality in CGD, reflecting the critical role for NADPH oxidase in antifungal host defense. Activation of NADPH oxidase in neutrophils can be coupled to the release of proteins and chromatin that comingle in neutrophil extracellular traps (NETs), which can augment extracellular antimicrobial host defense. NETosis can be driven by NADPH oxidase-dependent and -independent pathways. We therefore undertook an analysis of whether NADPH oxidase was required for NETosis in\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            pneumonia. Oropharyngeal instillation of live\n            <jats:named-content content-type=\"genus-species\">Aspergillus<\/jats:named-content>\n            hyphae induced neutrophilic pneumonitis in both wild-type and NADPH oxidase-deficient (p47\n            <jats:sup>\n              <jats:italic>phox\u2212\/\u2212<\/jats:italic>\n            <\/jats:sup>\n            ) mice which had resolved in wild-type mice by day 5 but progressed in p47\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n              \u2212\/\u2212\n            <\/jats:sup>\n            mice. NETs, identified by immunostaining, were observed in lungs of wild-type mice but were absent in p47\n            <jats:sup>\n              <jats:italic>phox<\/jats:italic>\n              \u2212\/\u2212\n            <\/jats:sup>\n            mice. Using bona fide NETs and nuclear chromatin decondensation as an early NETosis marker, we found that NETosis required a functional NADPH oxidase\n            <jats:italic>in vivo<\/jats:italic>\n            and\n            <jats:italic>ex vivo<\/jats:italic>\n            . In addition, NADPH oxidase increased the proportion of apoptotic neutrophils. Together, our results show that NADPH oxidase is required for pulmonary clearance of\n            <jats:named-content content-type=\"genus-species\">Aspergillus<\/jats:named-content>\n            hyphae and generation of NETs\n            <jats:italic>in vivo<\/jats:italic>\n            . We speculate that dual modulation of NETosis and apoptosis by NADPH oxidase enhances antifungal host defense and promotes resolution of inflammation upon infection clearance.\n          <\/jats:p>","DOI":"10.1128\/iai.00096-14","type":"journal-article","created":{"date-parts":[[2014,2,19]],"date-time":"2014-02-19T01:47:10Z","timestamp":1392774430000},"page":"1766-1777","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":153,"title":["NADPH Oxidase Promotes Neutrophil Extracellular Trap Formation in Pulmonary Aspergillosis"],"prefix":"10.1128","volume":"82","author":[{"given":"Marc","family":"R\u00f6hm","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research (MIMS), Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C.","family":"D'Auria","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos G.","family":"Almyroudis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA"},{"name":"Department of Medicine, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brahm H.","family":"Segal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA"},{"name":"Department of Medicine, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA"},{"name":"Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin F.","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research (MIMS), Ume\u00e5 University, Ume\u00e5, 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