Cell biology of Candida albicans-host interactions

Abstract

Candida albicans is a commensal coloniser of most people and a pathogen of the immunocompromised or patients in which barriers that prevent dissemination have been disrupted. Both the commensal and pathogenic states involve regulation and adaptation to the host microenvironment. The pathogenic potential can be downregulated to sustain commensalism or upregulated to damage host tissue and avoid and subvert immune surveillance. In either case it seems as though the cell biology of this fungus has evolved to enable the establishment of different types of relationships with the human host. Here we summarise latest advances in the analysis of mechanisms that enable C. albicans to occupy different body sites whilst avoiding being eliminated by the sentinel activities of the human immune system.

Figure 1

Candida virulence factors. Virulence is a polygenic trait in C. albicans involving biochemical, physiological, genetic and morphogenetic characteristics.

Figure 2

Interaction of C. albicans with macrophages showing the stages at which the fungus can deploy immune avoidance mechanisms. The macrophage uses chemotaxis to target the fungal cell, then fungus recognition and engulfment take place via interaction of fungal PAMPs and a series of immune cell PRRs that includes phagocytic receptors. The Candida cell is delivered to the phagosomal vesicle which undergoes fusion with lysosomes to create the mature acidic phagolysosome that can kill the fungal cargo using oxidative and nitrosative elements. However, C. albicans has the capacity to interfere with the phagolysomal maturation programme, increase its alkalinity, generate protective antioxidants and induce its own non-lytic expulsion. In addition, hypha formation and induced pyroptosis can cause the lysis of the phagocyte.

Figure 3

C. albicans interaction with host cells. [a] I invasion into oral epithelium with hyphae that have penetrated the host cells marked (*). [b] Phagocytosis by mouse peritoneal macrophages with extracellular parts of C. albicans stained with an anti-Candida Ab in green and counterstained with CFW in blue. The macrophages are stained red with phalloidin (F-actin) to visualize phagocytic uptake. [c] Human peripheral blood mononuclear cells aggregated around yeast cells and hyphae of C. albicans.