Candida albicans causes oral-cavity disease in a large number of patients. Den-ture stomatitis, angular chelitis (perliche), leukoplakia, glossitis, dental caries and possibly periodontal disease are a few examples. Very little is known about immunity to these diseases. Recent work from our laboratory demonstrated that C. albicans readily colonizes the alimentary tract of germfree athymic or euthymic mice, but mucosal infection (i.e. hyphal penetration of alimentary tract tissues) was minimal and was observed in keratinized epithelium of the stomach and on the dorsal tongue surface (rhomboid glossitis). Conversely, for the first time in a murine model, we have recently demonstrated that alimentary tract colonization of congenitally immunodeficient beige-nude (bg/bg-nu/nu) gnotobiotic mice with C. albicans results in massive infections of the oral-cavity, esophagus, stomach, internal organs and deaths (30% lethality in 2-4 weeks). Mice, isogeneic and heterozygous for the nude mutation (i.e. bg/bg-euthymic) do not die following colonization and they do not manifest severe candidiasis of the oral-cavity. These gnotobiotic Candida-monoassociated (MA) congenitally immunodeficient (CI) mice and their isogeneic immunocompetent (IC) counterparts will be used for the following studies. We will: 1) Characterize (culture and histology) and contrast the susceptibility of CI and IC gnotobiotic mice to mucosal candidiasis; 2) quantitate the antibody (serum and secretory) and cell-mediated immune responses (lymphocyte blastogenesis and footpad swelling to Candida antigens) that occur after germfree CI and IC mice are colonized and infected with C. albicans; and 3) we will delineate the relative importance of innate and acquired (antibody- and cell-mediated) immunity in resistance to mucosal and systemic candidiasis by specifically impairing or enhancing immune mechanisms in gnotobiotic CI and IC mice. These unique, gnotobiotic, congenitally immunodeficient mice will for the first time not only permit us to study host-Candida interactions on mucosal surfaces, but this research will allow us to delineate the specific immune mechanisms that are important for innate or acquired (cellular or humoral) resistance to oral-cavity candidiasis of endogenous origin.
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