Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

Damage response framework curves. Individual graphs are included for each class, with an associated Candida infection. (A) Class 1, pathogens that cause damage only in situations of weak immune responses (e.g., oral candidiasis). (B) Class 2, pathogens that cause damage either in hosts with weak immune responses or in the setting of normal immune responses (e.g., invasive candidiasis). (C) Class 3, pathogens that cause damage in the setting of appropriate immune responses and produce damage at both ends of the continuum of immune responses (e.g., intra-abdominal candidiasis). (D) Class 4, pathogens that cause damage primarily at the extremes of both weak and strong immune responses (e.g., gastrointestinal candidiasis). (E) Class 5, pathogens that cause damage across the spectrum of immune responses, but damage can be enhanced by strong immune responses (e.g., denture stomatitis). (F) Class 6, microorganisms that can cause damage only under conditions of strong immune responses (e.g., vaginal candidiasis). (Adapted from reference 1 with permission.)

Clinical manifestations of oral candidiasis. (A) Pseudomembranous candidiasis is characterized by white plaques formed on the tongue and the buccal mucosa. (B) Erythematous candidiasis example, showing the subtle red lesions on the tongue, which can also occur on the palate.

Mouse model of oral candidiasis. (A) An infected mouse exhibiting clinical signs of advanced candidiasis on the surface of the tongue 4 days post-sublingual infection with C. albicans. (B) Histopathology of an infected tongue tissue section, demonstrating the extensive presence of C. albicans around the periphery of the tongue. Hyphae can be seen penetrating the subepithelial tissue, along with a marked presence of host inflammatory cells. (C) Magnified image of tongue tissue, revealing the depth of hyphal invasion into the subepithelium (arrows). Bar, 20 μm. (D) Scanning electron micrograph of excised tongue showing the thick biofilm formed on the outer epithelial surface consisting of C. albicans hyphae invading the subepithelium. (E) Higher-magnification image of the outer surface of the tongue showing the epithelium spiny layer with hyphae penetrating through the surface. (F) Significant gap in the tissue caused by hyphae invading from the sublingual area as it emerges through the tongue surface. (Reprinted from reference 166.)

Clinical manifestations of denture stomatitis. (A) Red inflammatory lesions formed on the denture-associated palatal tissue in a patient with a partial denture. (B) Inflammation of the gingival tissue in a patient with a full denture.