{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:04:22Z","timestamp":1790413462245,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"PASPA-DGAPA-UNAM"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune defects in chronic pulmonary aspergillosis (CPA) are poorly characterized. We compared peripheral blood cytokine profiles in patients with CPA versus healthy controls and explored the relationship with disease severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Interferon-gamma (IFN\u03b3), interleukin (IL)-17, tumor necrosis factor-\u03b1, IL-6, IL-12, and IL-10 were measured after in vitro stimulation of whole blood with lipopolysaccharide (LPS), phytohemagglutinin, \u03b2-glucan, zymosan (ZYM), IL-12 or IL-18, and combinations. Clinical parameters and mortality were correlated with cytokine production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cytokine profiles were evaluated in 133 patients (57.1% male, mean age 61 years). In comparison to controls, patients with CPA had significantly reduced production of IFN\u03b3 in response to stimulation with \u03b2-glucan\u2005+\u2005IL-12 (312 vs 988 pg\/mL), LPS\u2005+\u2005IL-12 (252 vs 1033 pg\/mL), ZYM\u2005+\u2005IL-12 (996 vs 2347 pg\/mL), and IL-18\u2005+\u2005IL-12 (7193 vs 12\u00a0330 pg\/mL). Age\u2005&amp;gt;60 (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.00\u20132.91; P\u2005=\u2005.05) and chronic obstructive pulmonary disease (HR, 1.69; 95% CI, 1.03\u20132.78; P\u2005=\u2005.039) were associated with worse survival, whereas high IFN\u03b3 production in response to beta-glucan\u2005+\u2005IL-12 stimulation (HR, 0.48; 95% CI, .25\u20130.92; P\u2005=\u2005.026) was associated with reduced mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with CPA show impaired IFN\u03b3 production in peripheral blood in response to stimuli. Defective IFN\u03b3 production ability correlates with worse outcomes. Immunotherapy with IFN\u03b3 could be beneficial for patients showing impaired IFN\u03b3 production in CPA.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiab583","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T20:14:15Z","timestamp":1637871255000},"page":"1822-1831","source":"Crossref","is-referenced-by-count":25,"title":["Defective Interferon-Gamma Production Is Common in Chronic Pulmonary Aspergillosis"],"prefix":"10.1093","volume":"225","author":[{"given":"Stefano A P","family":"Colombo","sequence":"first","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rola","family":"Hashad","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom"},{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Alexandria University, Alexandria, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Denning","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinakantha S","family":"Kumararatne","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Immunology, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Ceron-Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Immunology, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Barcenas-Morales","sequence":"additional","affiliation":[{"name":"Laboratorio 2 de Inmunologia, FES-Cuautitlan, UNAM, Cuautitlan, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Manchester Collaborative Centre for Inflammation Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Harris","sequence":"additional","affiliation":[{"name":"National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Doffinger","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Immunology, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0662-1265","authenticated-orcid":false,"given":"Chris","family":"Kosmidis","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health 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