Immunosurveillance of Candida albicans commensalism by the adaptive immune system

Abstract

The fungal microbiota (mycobiota) is an integral part of the microbial community colonizing the body surfaces and is involved in many key aspects of human physiology, while an imbalance of the fungal communities, termed fungal dysbiosis, has been described in pathologies ranging from infections to inflammatory bowel disease. Commensal organisms, such as the fungus Candida albicans, induce antigen-specific immune responses that maintain immune homeostasis. Adaptive immune mechanisms are vital in this process, while deficiencies in adaptive immunity are linked to fungal infections. We start to understand the mechanisms by which a shift in mycobiota composition, in particular in C. albicans abundance, is linked to immunopathological conditions. This review discusses the mechanisms that ensure continuous immunosurveillance of C. albicans during mucosal colonization, how these protective adaptive immune responses can also promote immunopathology, and highlight therapeutic advances against C. albicans-associated disease.

Fig. 1. Adaptive immunity against C. albicans in health and disease.

(Left). Homeostatic immunity against C. albicans is maintained by cellular and humoral adaptive immunity. C. albicans drives fungus-specific and tissue-resident Th17 cells. IL-17 and IL-22 contribute to fungal control by promoting antimicrobial and barrier functions of the epithelium, the latter of which is counteracted by overt IFN-γ/STAT1-signalling. Antifungal Th17 immunity can also promote barrier defence against heterologous infections, both locally and systemically, and modulate social behaviour. Mucosal IgA targets fungal virulence determinants to repress C. albicans pathogenicity. C. albicans-specific IgG contributes to systemic antifungal immunity. (Right). Enhanced C. albicans-specific T cell and antibody responses have been observed in patients with gut barrier defects as in IBD. Whether IgA and Th17 cells act in a host-protective manner or whether antifungal T cells adopt features of pathogenic Th17 cells in the inflamed gut remains unclear. During airway inflammation, C. albicans-specific pathogenic Th17 cross-react with A. fumigatus. Enhanced C. albicans-reactive IgG antibodies have been associated with alcoholic and non-alcoholic liver disease, albeit their role in disease pathogenesis remains to be determined. See text for more details. The figure was generated with BioRender.com.