{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T19:41:46Z","timestamp":1784490106583,"version":"3.55.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic pulmonary aspergillosis (CPA) usually develops in patients with pre-existing lung damage. However, little is known about potential underlying immune defects that might predispose patients to developing this debilitating condition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed immunological analyses in 21 patients with CPA and 14 healthy controls. Polymorphonuclear granulocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated from venous blood. We measured reactive oxygen species (ROS) production and Aspergillus fumigatus killing capacity in PMNs and cytokine production by PBMCs in response to multiple stimuli after 24\u2005hours (TNF-\u03b1, IL-1\u03b2, IL-6, and IL-1RA) and 7 days (IFN-\u03b3, IL-17, and IL-22) by enzyme-linked immunosorbent assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients demonstrated no defects in PMN ROS production and A. fumigatus killing capacity as compared to controls. PBMC production of TNF-\u03b1, IL-1\u03b2, and IL-6 did not differ significantly between both groups in response to all but one stimulus. However, IL-1RA production was significantly higher in patients in response to several stimuli. Patients demonstrated deficient IFN-\u03b3 production in response to several stimuli and a decreased IL-17 response to phytohemagglutinin.<\/jats:p>\n                    <jats:p>Costimulation with A. fumigatus and M. avium leads to a synergistic TNF-\u03b1 response in healthy controls, but synergism was lost in patients with CPA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The impaired IFN-\u03b3 and (more restricted) IL-17 response found in patients with CPA indicates an adaptive immunity\/lymphocyte defect. Patients produce higher concentrations of the anti-inflammatory cytokine IL-1RA and demonstrate loss of synergistic TNF-\u03b1 production after costimulation with A. fumigatus and M. avium. No significant innate immune response defects were found in patients with CPA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf596","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T13:01:41Z","timestamp":1764075701000},"page":"573-582","source":"Crossref","is-referenced-by-count":1,"title":["Interferon-gamma Production Defects Characterize Immune Responses in Patients With Chronic Pulmonary Aspergillosis"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9629-8627","authenticated-orcid":false,"given":"Nico A F","family":"Janssen","sequence":"first","affiliation":[{"name":"Radboudumc\u2014CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]},{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5353-7691","authenticated-orcid":false,"given":"Mariolina","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Berk","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The \u00a0","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-5103","authenticated-orcid":false,"given":"Monique H E","family":"Reijers","sequence":"additional","affiliation":[{"name":"Radboudumc\u2014CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]},{"name":"Department of Pulmonology, Radboud University Medical Center , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-8030","authenticated-orcid":false,"given":"Agostinho","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho , Braga ,","place":["Portugal"]},{"name":"ICVS\/3B's-PT Government Associate Laboratory , Braga\/Guimar\u00e3es ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J M","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Radboudumc\u2014CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]},{"name":"Department of Pharmacy, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8600-9860","authenticated-orcid":false,"given":"Paul E","family":"Verweij","sequence":"additional","affiliation":[{"name":"Radboudumc\u2014CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]},{"name":"Department of Medical Microbiology, Radboud University Medical Center , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-9651","authenticated-orcid":false,"given":"Intan M W","family":"Dewi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1121-4894","authenticated-orcid":false,"given":"Frank L","family":"van de Veerdonk","sequence":"additional","affiliation":[{"name":"Radboudumc\u2014CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]},{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The \u00a0","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"2026031710042916600_jiaf596-B1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nrmicro.2017.90","article-title":"Aspergillus fumigatus morphology and dynamic host interactions","volume":"15","author":"van de Veerdonk","year":"2017","journal-title":"Nat Rev Microbiol"},{"key":"2026031710042916600_jiaf596-B2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1183\/13993003.00583-2015","article-title":"Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and 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