Adaptive immunity induces mutualism between commensal eukaryotes

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• Pathogenic fungi are part of the gut microbiota but rarely cause disease.
• Interactions between gut fungi and the host immune system that maintain mutualism are poorly understood.

Purpose of the Study:

• To investigate the role of adaptive immunity in promoting beneficial interactions between gut fungi and the host.
• To understand how intestinal immunoglobulin A (IgA) influences the relationship between Candida species and the host immune system.

Main Methods:

• Studied immune responses to potentially pathogenic Candida species in the gut.
• Focused on Candida albicans, examining the effects of IgA on its hyphal form and cell-surface adhesins.
• Utilized a vaccine to induce adhesin-specific immunity in mice and assessed protection against C. albicans-induced damage during colitis.

Main Results:

• Potentially pathogenic Candida species induce and are targeted by intestinal IgA responses.
• Intestinal IgA specifically targets and suppresses the pathogenic hyphal morphotype of Candida albicans by binding to hyphal-enriched adhesins.
• Immune selection against hyphae enhances the competitive fitness of C. albicans in the gut.
• C. albicans hyphae and IgA-targeted adhesins exacerbate intestinal damage during colitis.
• Vaccination-induced adhesin-specific immunity protects against C. albicans-associated damage during colitis.

Conclusions:

• Adaptive immunity, particularly IgA, plays a crucial role in suppressing harmful fungal effectors while allowing beneficial colonization.
• IgA decouples fungal colonization from pathogenesis, promoting gut homeostasis.
• Targeting fungal adhesins with vaccines can protect against fungal-associated intestinal damage.