An In Vivo Study On The Effect Of Farnesol On Oral Mucosal Infection Of Candida Albicans In Mice

Objective: First to establish a murine oral mucosal candidiasis model,observe oral mucosal infection and examine the corresponding systemic infection dynamically.Furthermore,to study the possible role of farnesol in the regulation of T cell and macrophage cytokine expression during murine oral mucosal candidiasis,and to explore the effects of farnesol combined with antifungal drugs on murine oral mucosal candidiasis.Methods:C.albicans were inoculated in the immunosuppressed mice using the oral swabs.Lesions in the murine tongue were observed using macroscopic observation.The viable cells of the C.albicans in the oral cavity were calculated and the histological study of the murine tongues was analyzed to determine C.albicans infections of the oral mucosal.Weight and fungal burdens in the kidney,liver and feces from the descending colon were examined to assess the severity of the systemic infections.Subsequently,enzyme-linked immunosorbent assay was used to determine the expression of cytokines IL-17,IFN-?,and TNF-? in the serum of mice infected orally by Candida albicans with different concentrations of farnesol and the above results were compared with the normal control group to expore the effect of farnesol on immune responses in mice.The viable cells of the C.albicans in the oral cavity and lesions on the murine tongue were examined,and the tissue of the infected tongue was analyze using histological examination to assess the potential therapeutic of combination of farnesol and antifungal drugs,in the treatment of murine oral candidiasis caused by either C.albicans clinical isolate AN106 or C.albicans SC5314.Results Experiment 1:The murine oral mucosal candidiasis model was successfully established.Lesions in the murine tongue,viable cells of the C.albicans in the oral cavity and other indicators detected that the model tended to stabilize within 3 to 5 days of infection.Experiment 2:The IL-17 expression of the high concentration of farnesol-treated group(100 ?M,300 ?M)was lower than that of the control group and the difference was significant(P<0.05).No significant difference was found in the expression of IFN-? and TNF-? in the farnesol treated group(,100 ?M,300 ?M),expression IL-17,IFN-?,and TNF-? in the farnesol treated group(10 ?M,50 ?M)compared with the control group.Experiment 3:The co-application of farnesol(8 ?M)potentiated the therapeutic performance of itraconazole for mice infected with either strain.It caused a statistically significant decrease in C.albicans cfu isolated from the oral cavity of the infected mice and reduced oral lesions.Compared with the control group,there was a statistical difference(P<0.05).The pathological section of the murine tongue with both farnesol and itraconazole showed normal tongue papillae and fewer hyphae.Farnesol(50 ?M)enhanced the therapeutic activity of nystatin against oral candidiasis in mice caused by clinical isolate AN106.Compared with the control group,there was a statistical difference(P<0.05).Farnesol(10 ?M,50 ?M)also enhanced the therapeutic activity of fluconazole against oral candidiasis in mice caused by standard strains S5314.Compared with the control group,there was a statistical difference(P<0.05).Conclusions: Inoculating C.albicans in the oral cavity of mice using oral swabs can establish a murine oral mucosal candidiasis model.The oral candidiasis of the infected mice was changed in a week.The appropriate time of animal experiments should have been chosen depending on the infection status.High concentrations of farnesol inhibited the normal expression of T cell cytokines IL-17 during oral mucosal infection of Candida albicans The combination of farnesol and antifungal drugs has synergistic effect on standard strains and clinical isolate oral candidiasis and has potential therapy.