Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies.

TitleHuman gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies.
Publication TypeJournal Article
Year of Publication2021
AuthorsDoron, I, Leonardi, I, Li, XV, Fiers, WD, Semon, A, Bialt-DeCelie, M, Migaud, M, Gao, IH, Lin, W-Y, Kusakabe, T, Puel, A, Iliev, ID
JournalCell
Date Published2021 Feb 01
ISSN1097-4172
Abstract

Antibodies mediate natural and vaccine-induced immunity against viral and bacterial pathogens, whereas fungi represent a widespread kingdom of pathogenic species for which neither vaccine nor neutralizing antibody therapies are clinically available. Here, using a multi-kingdom antibody profiling (multiKAP) approach, we explore the human antibody repertoires against gut commensal fungi (mycobiota). We identify species preferentially targeted by systemic antibodies in humans, with Candida albicans being the major inducer of antifungal immunoglobulin G (IgG). Fungal colonization of the gut induces germinal center (GC)-dependent B cell expansion in extraintestinal lymphoid tissues and generates systemic antibodies that confer protection against disseminated C. albicans or C. auris infection. Antifungal IgG production depends on the innate immunity regulator CARD9 and CARD9CX3CR1 macrophages. In individuals with invasive candidiasis, loss-of-function mutations in CARD9 are associated with impaired antifungal IgG responses. These results reveal an important role of gut commensal fungi in shaping the human antibody repertoire through CARD9-dependent induction of host-protective antifungal IgG.

DOI10.1016/j.cell.2021.01.016
Alternate JournalCell
PubMed ID33548172