phaidra.vetmeduni.ac.at o:5374 DOI 10.1016/j.mucimm.2025.11.006 Iron-Dependent allergenicity of Alt a 1: A link between fungal nutritional immunity and allergic sensitization The major fungal allergen Alt a 1 from Alternaria alternata is linked to allergic asthma. We assessed its biological role in nutritional immunity to iron and its allergenic potential using in silico, in vitro, and in vivo approaches. Alternaria was cultured with or without iron and with quercetin to promote iron-quercetin (FeQ2) complexes, followed by Alt a 1 expression analysis, which revealed enhanced expression under iron deficiency and reduced levels by addition of quercetin. In silico and RBLsx38 mast cell degranulation assays showed that FeQ2 binding to Alt a 1 (holoAlt a 1) masked the IgE epitope Y87-D96 by promoting tetramer-formation of Alt a 1, reducing IgE binding and antigen-specific degranulation compared to ligand-free Alt a 1 (apoAlt a 1). In BALB/c mice, intranasal exposure to apo- or holoAlt a 1 before intraperitoneal Alt a 1/alum sensitization demonstrated that holoAlt a 1 exposure led to lower allergen-specific antibody titers, fewer mature antigen-presenting cells, increased regulatory T cells, and reduced allergic symptoms upon challenge compared to mice exposed to apoAlt a 1. Additionally, human PBMCs incubated with holoAlt a 1 exhibited fewer Th cells and plasmablasts, but more immature B cells with a higher iron content than those exposed to apoAlt a 1. These findings demonstrate that iron-poor conditions trigger nutritional immunity in Alternaria, increasing Alt a 1 expression, and that apoAlt a 1, through iron scavenging, has greater sensitizing capacity than the holo form, influencing immune responses relevant to allergic asthma. eng 2026-07-27T10:04:03.854Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Fakhimahmadi;Aila; FN:Aila Fakhimahmadi X-ORCID:https://orcid.org/0000-0002-6804-6238 END:VCARD BEGIN:VCARD VERSION:3.0 N:Hufnagl;Karin; FN:Karin Hufnagl X-ORCID:https://orcid.org/0000-0002-2288-2468 END:VCARD BEGIN:VCARD VERSION:3.0 N:Hasanaj;Ilir; FN:Ilir Hasanaj END:VCARD BEGIN:VCARD VERSION:3.0 N:Szepannek;Nathalie; FN:Nathalie Szepannek END:VCARD BEGIN:VCARD VERSION:3.0 N:Hofstetter;Gerlinde; FN:Gerlinde Hofstetter X-ORCID:https://orcid.org/0000-0003-2077-4479 END:VCARD BEGIN:VCARD VERSION:3.0 N:Wiederstein;Markus; FN:Markus Wiederstein END:VCARD BEGIN:VCARD VERSION:3.0 N:Jensen;Sebastian A; FN:Sebastian A Jensen END:VCARD BEGIN:VCARD VERSION:3.0 N:Berger;Markus; FN:Markus Berger END:VCARD BEGIN:VCARD VERSION:3.0 N:Gorfer;Markus; FN:Markus Gorfer END:VCARD BEGIN:VCARD VERSION:3.0 N:Pogner;Clara E.; FN:Clara E. Pogner END:VCARD BEGIN:VCARD VERSION:3.0 N:Bianchini;Rodolfo; FN:Rodolfo Bianchini X-ORCID:https://orcid.org/0000-0003-0351-6937 END:VCARD BEGIN:VCARD VERSION:3.0 N:Pali-Schöll;Isabella; FN:Isabella Pali-Schöll END:VCARD BEGIN:VCARD VERSION:3.0 N:Jensen-Jarolim;Erika; FN:Erika Jensen-Jarolim X-ORCID:https://orcid.org/0000-0003-4019-5765 END:VCARD BEGIN:VCARD VERSION:3.0 N:Roth-Walter;Franziska; FN:Franziska Roth-Walter X-ORCID:https://orcid.org/0000-0001-5005-9228 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 11173752 https://phaidra.vetmeduni.ac.at/o:5374 https://phaidra.vetmeduni.ac.at/api/object/o:5374/thumbnail LOMv1.0 discipline