{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:08:07Z","timestamp":1792786087416,"version":"4.5.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione CARIT, Cassa di Risparmio di Terni e Narni"},{"name":"National Institute of Health","award":["R01CA244519"],"award-info":[{"award-number":["R01CA244519"]}]},{"name":"National Institute of Health","award":["R01CA259370"],"award-info":[{"award-number":["R01CA259370"]}]},{"name":"European Union's Horizon 2020 research and innovation program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The environmental light\/dark cycle has left its mark on the body's physiological functions to condition not only our inner biology, but also the interaction with external cues. In this scenario, the circadian regulation of the immune response has emerged as a critical factor in defining the host\u2013pathogen interaction and the identification of the underlying circuitry represents a prerequisite for the development of circadian-based therapeutic strategies. The possibility to track down the circadian regulation of the immune response to a metabolic pathway would represent a unique opportunity in this direction. Herein, we show that the metabolism of the essential amino acid tryptophan, involved in the regulation of fundamental processes in mammals, is regulated in a circadian manner in both murine and human cells and in mouse tissues. By resorting to a murine model of pulmonary infection with the opportunistic fungus Aspergillus fumigatus, we showed that the circadian oscillation in the lung of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO)1, generating the immunoregulatory kynurenine, resulted in diurnal changes in the immune response and the outcome of fungal infection. In addition, the circadian regulation of IDO1 drives such diurnal changes in a pre-clinical model of cystic fibrosis (CF), an autosomal recessive disease characterized by progressive lung function decline and recurrent infections, thus acquiring considerable clinical relevance. Our results demonstrate that the circadian rhythm at the intersection between metabolism and immune response underlies the diurnal changes in host\u2013fungal interaction, thus paving the way for a circadian-based antimicrobial therapy.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgad036","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T03:43:19Z","timestamp":1675395799000},"source":"Crossref","is-referenced-by-count":11,"title":["The circadian control of tryptophan metabolism regulates the host response to pulmonary fungal infections"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4432-1562","authenticated-orcid":false,"given":"Claudia","family":"Stincardini","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Pariano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"D\u2019Onofrio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Renga","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Orecchini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3113-0572","authenticated-orcid":false,"given":"Ciriana","family":"Orabona","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Nunzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gargaro","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fallarino","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Kook","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of California, Irvine (UCI) , Irvine, CA 92697 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget M","family":"Fortin","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of California, Irvine (UCI) , Irvine, CA 92697 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma","family":"Masri","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, University of California, Irvine (UCI) , Irvine, CA 92697 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8410-7248","authenticated-orcid":false,"given":"Stefano","family":"Brancorsini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigina","family":"Romani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Costantini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. Severi 1, 06132 Perugia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Maria","family":"Bellet","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia , P.le L. 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