We used an experimental model of oral candidiasis in the mouse to investigate the impact of the introduction of Candida albicans into a Candida-free system. We report that 2 strains of mice with the same major histocompatibility complex haplotype (H-2d) display different kinetics of primary oral infection after topical application of the same inoculum. The mucosal reactions in both DBA/2 and BALB/c mice involve a similar recruitment of CD4+ and CD8+ T cells and of MAC-1+ cells in mucosal tissue during the infection. A carrier state is maintained following the resolution of the infection in both strains and is associated with the persistence of intraepithelial CD4+ T cells. However, there is a time-specific recruitment of gamma delta T cells that coincides with a dramatic decrease in viable Candida in the mucosal tissue; this occurs on day 3 in BALB/c mice and on day 6 in DBA/2 mice. The denouement of an oral contact with Candida is also different in the 2 mouse strains, cell-mediated immunity being triggered in DBA/2 mice but not in BALB/c mice. The different kinetics of Candida clearance in BALB/c vs DBA/2 mice may therefore signal a differential priming of T cell subsets whose modalities do not appear to be associated with the H-2 complex.

While studying the oral bacterial biota of mice, we observed an unidentified streptococcus (TG) that eventually became the dominant species of the oral cavities of all other mice in our animal facility. We found that the strain is indigenous to Jackson Laboratory mice but is absent in animals from Charles River Laboratories. TG was also transmitted from artificially contaminated BALB/c mice to the oral cavities of 4 other mouse strains. Streptococcus sp. TG stimulated the secretory and systemic immune systems of artificially contaminated Charles River BALB/c mice but did not provoke clinical symptoms. The increase in antibody level to TG did not prevent its colonization and persistence in these mice. In mice from Jackson Laboratory, the secretory and systemic immune response to TG was significantly lower. In vitro, Streptococcus sp. TG inhibited murine oral lactobacilli and staphylococci, probably due to the production of hydrogen peroxide.

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The distribution of the resident oral bacterial species was evaluated in six genetically different mouse strains (BALB/c, C3H/He, C57BL/6, C57BL/10, DBAj2 and CD-1). The results indicate that these mouse strains harbour different oral microbiota upon arrival at our animal facilities. However, this difference persists only in strains C57BL/10 and DBAj2 1 wk after arrival. Except for strains CD-1 and C57BL/10, the oral biota is different upon arrival compared to that observed after 1 wk at our animal facilities. For the same mouse strain, the oral biota can differ significantly from one shipment to another upon arrival but tends to stabilise after 1 wk. This stabilising effect can be related to the increase in the proportion of Lactobacillus murinus among the total cultivable oral microbiota. These results indicate that if the host genetic background influences the distribution of the oral bacterial populations, its effect is masked by environmental factors.

Using an experimental model in the mouse we have shown that both local and central lines of defense, involving CD4+ T cells, participate in a dynamic interaction to maintain a long-term carrier state of Candida albicans in the oral cavity. We have tested the impact of a predisposing factor to oral candidiasis in the form of a topical application of a corticosteroid (Topsyn gel) to the oral mucosa for 75 mice twice a day for a 20-day period. Very rapidly after the treatment was initiated, i.e. on day 4, the residual population of Candida increased up to 40-fold and by day 21, the population was 400-fold that of the carrier state. The resident population of intraepithelial CD4+ T cells in the oral mucosa virtually disappeared during the treatment. A topical corticosteroid application also resulted in a massive depletion of T cells in the lymph nodes and in the transient abrogation of the DTH reaction to Candida antigens. On cessation of treatment, normal levels of both Candida and intraepithelial CD4+ T cells were also quickly restored. These results suggest that resistance to superficial invasion by Candida is linked to the presence of an oral mucosal line of defense and that topical application of corticosteroids may dramatically shift the host-parasite relationship in favor of Candida.

To assess the influence of pregnancy and lactation on the oral microbial ecology of BALB/c mice, we followed the distribution of the predominant oral bacteria of four groups of these mice during these two periods. Compared with nonpregnant control female mice of the same age maintained under the same conditions, the distribution of the resident oral bacterial species differed significantly only during the lactation period (8-16 days after parturition). This difference could possibly be attributed to hormonal influences and/or grooming habits.