Innate Immunity and Saliva in Candida albicans-mediated Oral Diseases

Abstract

The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals.

Keywords: antimicrobial proteins; microbial dysbiosis; mucosal immunity; oral microbiota; oropharyngeal candidiasis; salivary dysfunction.

Figure 1.

Candida albicans morphologies involved in oropharyngeal candidiasis. C. albicans can exist in the yeast form (left, top) that can transition into a more virulent hyphal form (left, bottom). Both morphologies are present in biofilms (right) that are found on mucosal surfaces in oropharyngeal candidiasis.

Figure 2.

Oral manifestations of oropharyngeal candidiasis. White plaques comprising Candida albicans yeast and hyphal forms can be seen on the tongue (left) and the buccal mucosa and soft palate (right) during oropharyngeal candidiasis.

Figure 3.

Role of salivary proteins in oropharyngeal candidiasis. Salivary proteins (proline-rich proteins [PRPs], statherins, mucins) and oral epithelial transglutaminase (Tgase) can aid Candida albicans growth by promoting adherence to oral tissues or inhibiting growth through immune exclusion by binding and aggregating fungal cells (mucins and secretory IgA [sIgA]) to facilitate their clearance by swallowing. Antifungal proteins, including salivary histatin 5 (Hst 5) or calprotectin and β-defensins (secreted by oral tissues), prevent C. albicans growth.