{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:50:39Z","timestamp":1785408639459,"version":"3.56.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22fk0108530h0001"],"award-info":[{"award-number":["22fk0108530h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["A48 and A90"],"award-info":[{"award-number":["A48 and A90"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K07941"],"award-info":[{"award-number":["23K07941"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020961","name":"Support Program for Starting up Innovation Hub","doi-asserted-by":"publisher","award":["JPMJST2281"],"award-info":[{"award-number":["JPMJST2281"]}],"id":[{"id":"10.13039\/501100020961","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["16K08844, 23K06677, JP223fa627004"],"award-info":[{"award-number":["16K08844, 23K06677, JP223fa627004"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Invasive aspergillosis in immunocompromised individuals is associated with a poor prognosis. Recently, the global emergence of azole-resistant\n                      <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                      has underscored the urgent need for novel therapeutic strategies beyond conventional small-molecule antifungal agents. Natural killer (NK) cells, which are characterized by the absence of CD3 and presence of CD56 surface markers, play a pivotal role in the immune response against fungal pathogens and in the elimination of malignant cells and virus-infected host cells. Although the antifungal activity of NK cells against\n                      <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic>\n                      spp. and other fungi has been demonstrated, the efficacy of\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      -expanded human NK cells against azole-resistant\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      has not been investigated. NK cells, which were expanded from the CD3\n                      <jats:sup>\u2212<\/jats:sup>\n                      peripheral blood mononuclear cells obtained from healthy donors, were co-cultured with fungi. Antifungal activity was assessed using the 2,3-(bis2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide reduction assay. NK cells demonstrated antifungal activity against azole-resistant\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      and other filamentous fungi. These findings suggest that a direct interaction between NK cells and hyphae is critical for exerting antifungal effects, with degranulation likely contributing to the underlying mechanism. However, contrary to previous reports, we failed to observe the direct antifungal activity of interferon-\u03b3 secreted by NK cells under our experimental conditions. Cellular immunotherapy using NK cells may represent a promising therapeutic approach for the treatment of azole-resistant aspergillosis.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                        is a ubiquitous fungus that causes invasive aspergillosis (IA) in immunocompromised patients, with poor prognosis. Furthermore, azole-resistant\n                        <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                        has spread globally in recent years. The present antifungal drugs pose challenges such as drug resistance and adverse events; thus, the development of novel therapies for IA is needed beyond the antifungal drugs. In cases of IA in immunocompromised patients with poor response to antifungal drugs, cellular immunotherapy is a reasonable approach. This study demonstrated that human natural killer (NK) cells derived from peripheral blood exhibit antifungal activity against azole-resistant\n                        <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                        comparable to that of azole-susceptible strain. This indicates that cellular immunotherapy using NK cells could become an effective therapy for IA caused by azole-resistant\n                        <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                        . Investigating the mechanism by which NK cells exhibit antifungal activity against\n                        <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                        could lead to the development of novel therapies for IA.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03372-25","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T13:23:09Z","timestamp":1776777789000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Human natural killer cells exhibit potent antifungal activity against azole-resistant\n                    <i>Aspergillus fumigatus<\/i>\n                    and diverse filamentous 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