2026-08-23T19:31:45Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1294832025-12-20T00:53:31Zcom_20.500.14352_14col_20.500.14352_15

Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn's disease Doron, Itai Mesko, Marissa Li, Xin V. Kusakabe, Takato Leonardi, Irina Shaw, Dustin G. Fiers, William D. Lin, Woan-Yu Bialt-DeCelie, Meghan Román González, Elvira Longman, Randy S. Pla Alonso, Jesús Wilson, Patrick C. Iliev, Iliyan D. 579 Fungal host response Mucosal immunology Microbiología (Farmacia) 2414 Microbiología 3201 Ciencias Clínicas Secretory immunoglobulin A (sIgA) plays an important role in gut barrier protection by shaping the resident microbiota community, restricting the growth of bacterial pathogens and enhancing host protective immunity via immunological exclusion. Here, we found that a portion of the microbiota-driven sIgA response is induced by and directed towards intestinal fungi. Analysis of the human gut mycobiota bound by sIgA revealed a preference for hyphae, a fungal morphotype associated with virulence. Candida albicans was a potent inducer of IgA class-switch recombination among plasma cells, via an interaction dependent on intestinal phagocytes and hyphal programming. Characterization of sIgA affinity and polyreactivity showed that hyphae-associated virulence factors were bound by these antibodies and that sIgA influenced C. albicans morphotypes in the murine gut. Furthermore, an increase in granular hyphal morphologies in patients with Crohn's disease compared with healthy controls correlated with a decrease in antifungal sIgA antibody titre with affinity to two hyphae-associated virulence factors. Thus, in addition to its importance in gut bacterial regulation, sIgA targets the uniquely fungal phenomenon of hyphal formation. Our findings indicate that antifungal sIgA produced in the gut can play a role in regulating intestinal fungal commensalism by coating fungal morphotypes linked to virulence, thereby providing a protective mechanism that might be dysregulated in patients with Crohn's disease. Ministerio de Economía y Competitividad (España) Comunidad de Madrid US National Institutes of Health Leona M. and Harry B. Helmsley Charitable Trust (United States) Irma T. Hirschl Career Scientist Award (United States) Crohn’s and Colitis Foundation (United States) Pilot Project Funding from the Center for Advanced Digestive Care (United States) Burrough Welcome Trust PATH Award (United States) Depto. de Microbiología y Parasitología Fac. de Farmacia TRUE pub 2025-12-19T14:06:53Z 2025-12-19T14:06:53Z 2021 journal article AM https://hdl.handle.net/20.500.14352/129483 XXXX-XXXX 10.1038/s41564-021-00983-z eng PGC2018-095047-B-I00 info:eu-repo/grantAgreement/CAM/InGEMICs/B2017%2FBMD-3691 info:eu-repo/grantAgreement/NIH/R01AI163007 info:eu-repo/grantAgreement/NIH/R01DK113136 info:eu-repo/grantAgreement/NIH/R01DK121977 Doron I, Mesko M, Li XV, et al. Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn’s disease. Nat Microbiol 2021;6:1493–504. https://doi.org/10.1038/s41564-021-00983-z restricted access application/pdf Springer Nature