Friendly fungi: symbiosis with commensal Candida albicans

Abstract

Mucosal tissues are constitutively colonized by a wide assortment of host-adapted microbes. This includes the polymorphic fungus Candida albicans which is a primary target of human adaptive responses. Immunogenicity is replicated after intestinal colonization in preclinical models with a surprising array of protective benefits for most hosts, but harmful consequences for a few. The interaction between fungus and host is complex, and traditionally, the masking of antigenic fungal ligands has been viewed as a tactic for fungal immune evasion during invasive infection. However, we propose that dynamic expression of cell wall moieties, host cell lysins, and other antigenic C. albicans determinants is necessary during the more ubiquitous context of intestinal colonization to prime immunogenicity and optimize mammalian host symbiosis.

Keywords: Crohn's disease; airway hyper-reactivity; allergy; asthma; beta-glucan; colitis; fungal cell wall; inflammation; inflammatory bowel disease; mannan; mannoproteins; microbiome; mycobiome; symbiosis; ulcerative colitis.

Figure 1.. Model depicting how spatial dynamics may govern the immunogenicity of commensal fungi.

C. albicans and other fungal species lie in close approximation with the intestinal mucosa, whereas other fungi including Aspergillus, Wallemia, and Epicoccum species are more restricted to the intestinal lumen. Recent studies [65] show that administration of fluconazole to mice to selectively eradicate C. albicans promotes their susceptibility to DSS-induced intestinal inflammation which may involve less-host adapted luminal fungi species gaining access to the intestinal mucosa, and thereby causing local accumulation of acute inflammatory cells.

Figure 2.. Host-adapted C. albicans shows a range of host cell-damaging capacities and expression of host cell toxins linked with filamentation.

Recent studies show that C. albicans filamentation is associated with enhanced host cell-damaging capacity and immunogenicity [53, 69]. Expression of the fungal toxin candidalysin is linked to filamentation and contributes to the immunogenicity of C. albicans human clinical isolates with high macrophage cell-damaging capacity [69]. These results highlighting the heterogeneity in C. albicans suggest that colonization by fungal strains predisposed to filamentation and candidalysin production may increase susceptibility to aberrant inflammation consequences. By extension, colonization with fungal species that are likely to be even less host-adapted, and their access to the intestinal mucosa with fungal dysbiosis, might help explain the susceptibility to aberrant inflammation associated with the presence of non-Candida fungal species in the intestine of mice and humans [, , –67, 73].