Intestinal Candida albicans overgrowth in IgA deficiency

Abstract

Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, it remains unknown whether human IgA-deficiency is associated with gut fungal dysbiosis. Our goal was to study the impact of IgA on gut mycobiota ecology. The Fungi-flow method was used to characterize fecal, systemic, and maternal IgA, IgM and IgG responses against 14 representative fungal strains (yeast/spores or hyphae forms) in healthy donors (HD, n= 34, 31 and 20, respectively), and also to compare gut mycobiota opsonization by secretory antibodies in HD (n=28) and patients with selective IgA deficiency (SIgAd n=12). Stool mycobiota composition was determined by ITS gene sequencing in HD (n= 23) and SIgAd (n=17). Circulating CD4+ T cell cytokine secretion profiles were determined by intracellular staining. Impact of secretory IgA, purified from breast milk (n=9), on candida growth and intestinal Caco-2 cell invasion was tested in vitro. Homeostatic IgA binds commensal fungi with a body fluid-selective pattern of recognition. In SIgAd patients, fungal gut ecology is preserved by compensatory IgM binding to commensal fungi. Gut Candida albicans overgrowth nevertheless occurs in this condition, but only in clinically symptomatic patients with decreased Th17/22 T cell responses. Indeed, secretory IgA can reduce in vitro budding and invasion of intestinal cells by C. albicans, and therefore exert control on this pathobiont. IgA has a selective impact on C. albicans ecology to preserve fungal-host mutualism.