Title | Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Doron 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 |
Journal | Cell |
Volume | 184 |
Issue | 4 |
Pagination | 1017-1031.e14 |
Date Published | 2021 02 18 |
ISSN | 1097-4172 |
Keywords | Animals, Antibodies, Fungal, B-Lymphocytes, Candida albicans, Candidiasis, CARD Signaling Adaptor Proteins, Feces, Gastrointestinal Tract, Germinal Center, Humans, Immunity, Immunoglobulin G, Mice, Inbred C57BL, Mycobiome, Phagocytes, Polymorphism, Single Nucleotide, Protein Binding, Signal Transduction |
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 CARD9+CX3CR1+ 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. |
DOI | 10.1016/j.cell.2021.01.016 |
Alternate Journal | Cell |
PubMed ID | 33548172 |
PubMed Central ID | PMC7936855 |
Grant List | R01 AI127564 / AI / NIAID NIH HHS / United States R01 DK113136 / DK / NIDDK NIH HHS / United States R01 DK121977 / DK / NIDDK NIH HHS / United States R56 AI137157 / AI / NIAID NIH HHS / United States |