| Oral candidiasis is an acute, subacute or chronic oral mucosal diseases caused bycandida species. In recent years, due to the extensive application of antibiotics andimmunosuppressive agents in clinical which causes dysbacteriosis or Decreasedimmunity, the number of internal organs, skin and mucosal fungal infections is increasing,so as the incidence of oral mucosal candidiasis. Oral candidiasis can be divided intopseudomembranous type, atrophic type and proliferative type according to lesioncharacteristics and location. Common oral candidiasis includes Candida albicans cheilitisand angular cheilitis. There is the possibility of malignant transformation of chronic oralcandidiasis. The most important pathogens of oral candidiasis is candida albicans. Thisbacterium is oval budding yeast like fungi, gram-positive, rod-shaped, extending buddingcells resembling pseudohyphal Candida albicans hyphal, hence the name. Candida’sresistance is not strong to heat, but strong to dry, sunlight, ultraviolet radiation andchemical agents. Candida albicans is a typical opportunistic pathogen, usually notpathogenic when parasitic in vivo, and when it develops into the mycelia type, have thepathogenicity. The infection and pathogenic mechanism of Candida albicans mainlyincludes four steps: adhesion, germ tube and hyphal formation, secretion of protease,colony conversion. At present, the treatment of Candida albicans is mainly by localtherapy, but severe cases of chronic Candida infections often need to be supplementedwith systemic antifungal therapy to be effective. The common antifungal agents includenystatin, miconazole and fluconazole.T cell exercises its full impact on target cell through the combinatorial secretion ofcytokines. The newly elaborated Th22subsets of helper t cells cannot produce IFN-γ，IL-4and IL-17，but is characterized by the secretion of TNF-α and IL-22. Th22cellsbelong to a new class of leukocytes, with little or no direct effect on other immune cells,but selective effect on epithelial cells. The latest research results show that IL-22andTNF-α can synergisticly activate the innate immune response of keratinocytes in certain skin disorders (such as psoriasis, allergic eczema, etc.). This article mainly focuses onstudying whether TNF-α and IL-22have the similar activation mechanism in the Candidaalbicans infected oral mucosal epithelial cells, resulting in anti-fungal activity. To thisend, we first established a mouse Candida albicans oral infection model and on this basisproved that IL-22and TNF-α are the cytokines associated with innate immune responsein mice oral mucosal epithelial cells. Subsequently, in the primary human oral epithelialcells, we observed that IL-22and TNF-α have a synergistic effect on activation of theinnate immune response. IL-22could increase the number of several TNF-α dependentimmune regulatory factors, such as initial complement factor C1r and C1s, theantibacterial peptide S100A7and HBD-2(human βdefensin2) and induction andsecretion of chemotactic factor CXCL-9/-10/-11in human primary keratinocytes. Furtherstudy of intracellular signaling pathways reveal that such a coordination mechanism ofIL-22and TNF-α is mediated via the MAP kinase and its downstream intracellulartranscription factor AP-1family. By intraperitoneal injection of IL-22and TNF-α inmouse with oral infection of Candida albicans, mucosal injury can be significantlyreduced. In addition, the protective effect of IL-22and TNF-α on mucosal cells was alsoobserved in primary human oral mucosal epithelial cells infected with Candida albicans.In conclusion, we demonstrated that IL-22and TNF-α is a powerful combination ofcytokines in the mucosal immune. This provides a potential target for the development oforal mucosa antifungal drugs: IL-22. |
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