{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:19:57Z","timestamp":1785410397289,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,16]]},"group-title":"Immunology","reference-count":35,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R03HL154242 (KMR)"],"award-info":[{"award-number":["R03HL154242 (KMR)"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 HL146479 (RG)"],"award-info":[{"award-number":["R01 HL146479 (RG)"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["NIAID R01AI153337 (KMR)"],"award-info":[{"award-number":["NIAID R01AI153337 (KMR)"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Influenza-associated pulmonary aspergillosis (IAPA) is a severe complication of influenza infection associated with substantial mortality. Influenza disrupts pulmonary host defenses and alters innate immune responses, predisposing patients to invasive fungal infection. Interleukin-27 (IL-27) is an immunoregulatory cytokine with context-dependent antiviral and antifungal effects; however, its role during IAPA remains undefined. A mouse model of IAPA was established by infecting wild-type and IL-27 receptor \u03b1-deficient (\n                  <jats:italic>\n                    Il27ra\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/\n                    <jats:sup>\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  ) mice with influenza A, followed by\n                  <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                  challenge. IL-27 and IL-27R\u03b1 expression were increased during IAPA. Single-cell RNA sequencing identified monocytes as the primary source of IL-27 and T cells as major IL-27r\u03b1-expressing cells.\n                  <jats:italic>\n                    Il27ra\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/\n                    <jats:sup>\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  mice exhibited significantly increased pulmonary fungal and influenza viral burden, enhanced type 2 immune responses characterized by elevated IL-4, IL-5, IL-9, IL-13, eosinophils, Th2 cells, pathogenic Th2 cells, and ILC2s. Despite increased eosinophil abundance, eosinophil-mediated conidial killing was impaired in\n                  <jats:italic>\n                    Il27ra\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/\n                    <jats:sup>\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  mice. IL-27R\u03b1 deficiency also reduced macrophage abundance and impaired macrophage conidial uptake. Conversely, timed administration of rIL-27 enhanced fungal clearance, improved survival, and increased macrophage conidial uptake and augmented eosinophil killing capacity during IAPA. IL-27 signaling is a protective immunoregulatory cytokine during IAPA that limits pathological type 2 inflammation and enhances antifungal effector function of both eosinophils and macrophages. These findings identify IL-27 as a potential therapeutic in IAPA.\n                <\/jats:p>","DOI":"10.64898\/2026.07.10.737799","type":"posted-content","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:55:12Z","timestamp":1784260512000},"source":"Crossref","is-referenced-by-count":0,"title":["IL-27 Signaling Protects Against Influenza-Associated Pulmonary Aspergillosis Through Inhibition of Type 2 Immunity and Enhanced Antifungal Immunity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1943-0353","authenticated-orcid":false,"given":"Nima","family":"Naghshtabrizi","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0565-9299","authenticated-orcid":false,"given":"Yonne Karoline Ten\u00f3rio","family":"de Menezes","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0376-5395","authenticated-orcid":false,"given":"Ravineel B.","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dequan","family":"Lou","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6980-5454","authenticated-orcid":false,"given":"Kong","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-5744","authenticated-orcid":false,"given":"Radha","family":"Gopal","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caden","family":"Ngeow","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7896-6426","authenticated-orcid":false,"given":"Keven M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071910351082000_2026.07.10.737799v1.1","first-page":"37","article-title":"Estimates of US influenza-associated deaths made using four different methods. 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