Title | Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn's disease. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Doron, I, Mesko, M, Li, XV, Kusakabe, T, Leonardi, I, Shaw, DG, Fiers, WD, Lin, W-Y, Bialt-DeCelie, M, Román, E, Longman, RS, Pla, J, Wilson, PC, Iliev, ID |
Journal | Nat Microbiol |
Volume | 6 |
Issue | 12 |
Pagination | 1493-1504 |
Date Published | 2021 Dec |
ISSN | 2058-5276 |
Abstract | 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. |
DOI | 10.1038/s41564-021-00983-z |
Alternate Journal | Nat Microbiol |
PubMed ID | 34811531 |
PubMed Central ID | PMC8622360 |
Grant List | R01 AI163007 / AI / NIAID NIH HHS / United States R01 DK113136 / DK / NIDDK NIH HHS / United States R01 DK121977 / DK / NIDDK NIH HHS / United States AI163007 / / Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) / |