Fig. 1: C. albicans-elicited immune responses during eubiosis and dysbiosis. | Mucosal Immunology

Fig. 1: C. albicans-elicited immune responses during eubiosis and dysbiosis.

From: “Molding” immunity—modulation of mucosal and systemic immunity by the intestinal mycobiome in health and disease

Fig. 1

a Antibiotic-treatment and microbiome perturbations lead to fungal overgrowth and morphological changes in fungal colonizers. C. albicans morphological switch is mediated by master transcription factors (e.g., Efg1 and Wor1) that orchestrate gene expression and the transition from commensal yeast form to pathological hyphal growth.52,53 Commensal bacteria and secreted metabolic products (e.g., SCFA) suppress hyphae formation and can induce commensalism.29,31,32,35 Community disruption and release of bacterial cell wall components (e.g., peptidoglycans) allows for hyphal growth, associated with intestinal inflammation and extraintestinal dissemination.36,37 b During eubiosis, fungal interactions with the mucosal immune system induce tolerogenic and homeostatic immune responses. Fungal sensing by tolerogenic DCs induce IL-10 secretion and Tregs in intestinal lamina propria.82,83 Intestinal pathobionts also induce class switching and systemic release of antifungal IgG.24 Similarly, induced Th17 responses, and secreted cytokines IL-17 and IL-22 further contribute to barrier integrity by supporting mucus production, antimicrobial peptides (e.g., β-defensins), and immunoregulatory cytokines (e.g., TSLP and IL-6) released by epithelial cells.104,108,142,143,144 c Following microbiome disruption, hyphae formation allows for epithelial adhesion and cell damage, eliciting mucosal inflammation. Hyphae detection by inflammatory DCs induces Th2 responses and eosinophilia.82 Intestinal fungi uptake by cDC2 and CX3CR1+ MNP induces antibody class switch and secretory IgA towards the mycobiome.60 Hyphal cell recognition by NLRP3 inflammasome releases pro-inflammatory cytokines (e.g., IL-1β and IL-18) that support Th1 and Th17 differentiation.112,114,115 Additionally, candidalysin, the cytotoxic peptide secreted by C. albicans hyphal cells, induces epithelial damage and release of alarmins, further supporting antifungal inflammatory responses and neutrophilia in the intestinal lamina propria.103,104,108,112 SCFA short-chain fatty acids; PPG peptidoglycans; AMP antimicrobial peptides; DC dendritic cells; MNP mononuclear phagocytes; Treg regulatory T cells; Th T helper cell responses (type1, type 2, and type 17); TSLP thymic stromal lymphopoietin; Eos, eosinophils; Neut neutrophils; NLRP3 NOD-and pyrin domain-containing protein 3.

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