Experimental oral candidiasis in animal models

Abstract

Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data.

FIG. 1

Simplified schematic diagram comparing the topographic distribution of common lesional sites in human oral candidiasis (A) and experimental candidal infection in an animal model (rat/mouse/hamster) (B). The most common sites of infection are shaded. The clinical variants of the disease and their preponderant sites are as follows: 1, erythematous candidiasis; 2, pseudomembranous candidiasis; 3, hyperplastic candidiasis; 4, Candida-associated denture stomatitis; 5, Candida-associated angular chelitis; 6, Candida-associated median rhomboid glossitis.

FIG. 2

Macroscopic appearance of typical lesions observed on the dorsal surface of SD rat tongue infected with C. albicans after tetracycline and cyclophosphamide administration. Note the areas of hyperplasia or leukoplakia (arrows) and the conical papillae appearing as a crescent in between.

FIG. 3

Photomicrograph of a biopsy specimen illustrating the hyperplastic epithelial response to candidal invasion of the rat oral mucosa. Note the hyphal elements in the superficial layers. Periodic acid-Schiff stain. Magnification, ×40.

FIG. 4

Scanning electron micrographs of a depapillated lingual lesion observed in experimental candidiasis in a rat, resembling erythematous candidiasis of humans (magnification, ×38) (A) and the lesion showing a hyphal element of C. albicans penetrating the epithelium, together with a multitude of commensal bacteria (magnification, ×2,400) (B). Photographs provided courtesy of Carl M. Allen, College of Dentistry, Ohio State University.

FIG. 5

(A) Histopathologic section of leukoplakia on the dorsal tongue of an SD rat infected with C. albicans. Note the loss of filiform papillae and the flat-surfaced, parakeratotic, edematous and acanthotic lingual epithelium. (B) Photomicrograph of the lingual mucosa from the posterior dorsal tongue of an SD rat demonstrating uninfected epithelium. Note the normal filiform papillae covered by a layer of thick acellular orthokeratin. Hematoxylin and eosin stain. Magnifications, ×200.

FIG. 6

Histopathologic sections of depapillated areas on the dorsal tongue surface of two SD rats, showing epithelial invasion by C. albicans (5.00 to 17.71 μm) (A) and C. krusei (5.01 to 8.34 μm) (B) hyphal elements. Periodic acid-Schiff stain. Magnifications, ×400. Note the longer hyphal elements of C. albicans compared with C. krusei.