Intestinal Candida albicans overgrowth in IgA deficiency
Alicia Moreno‐Sabater, Delphine Sterlin, Lejla Imamovic, Fabienne Bon, Anne‐Cécile Normand, Cécile Gonnin, Marianne Gazzano, Merieme Bensalah, Karim Dorgham, E. Ben Salah, Aniss Acherar, Christophe Parizot, Virginie Rigourd, Hervé Bègue, Frédéric Dalle, Claude Bachmeyer, Christophe Hennequin, Hans Yssel, Marion Malphettes, Claire Fieschi, Jehane Fadlallah, Guy Gorochov
Abstract
Background Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, whether human IgA-deficiency is associated with gut fungal dysbiosis remains unknown. Objectives Our goal was to study the impact of IgA on gut mycobiota ecology. Methods 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 (HDs) (n = 34, 31, and 20, respectively) and to also compare gut mycobiota opsonization by secretory antibodies in HDs (n = 28) and patients with selective IgA deficiency (SIgAd) (n = 12). Stool mycobiota composition was determined by internal transcribed spacer gene sequencing in HDs (n = 23) and patients with SIgAd (n = 17). Circulating CD4 + T-cell cytokine secretion profiles were determined by intracellular staining. The impact of secretory IgA, purified from breast milk (n = 9), on Candida albicans growth and intestinal Caco-2 cell invasion was tested in vitro . Results Homeostatic IgA binds commensal fungi with a body fluid–selective pattern of recognition. In patients with SIgAd, fungal gut ecology is preserved by compensatory IgM binding to commensal fungi. Gut C albicans overgrowth nevertheless occurs in this condition but only in clinically symptomatic patients with decreased T H 17/T H 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. Conclusion IgA has a selective impact on C albicans ecology to preserve fungal-host mutualism.