ABSTRACT
BACKGROUND: Trichophyton-induced superficial skin mycosis is a common infectious human disease, but the immunological mechanism against Trichophyton infection is unclear with regard to many points. Since Trichophyton cannot colonize mice, guinea pigs were used in previous experiments on Trichophyton infection. However, it is difficult to perform immunological and genetic analyses in guinea pigs. OBJECTIVE: The objective of this study was to establish a mouse Trichophytin-associated inflammation model of superficial skin mycosis in which immunological and genetic analyses can be performed. METHODS: We established a mouse Trichophyton-induced contact hypersensitivity model by applying Trichophytin, the Trichophyton antigen, extracted from Trichophyton mentagrophytes, to mice. Using a Th1-dominant strain, C57BL/6, and a Th2-dominant strain, BALB/c, we investigated the expression of inflammatory cytokines and receptors of the innate immune system for fungi, TLR4, TLR2, and dectin-1, and their influences on responses of the acquired immune system. RESULTS: In C57BL/6 mice, expressions of IFN-γ and IL-17 A in regional lymph nodes and IL-1ß, IFN-γ, IL-6, and IL-23 in the inflammatory auricular skin were enhanced by Trichophytin challenge, suggesting that not only Th1 cells but also Th17 cells were induced. In BALB/c mice, expressions of IL-4 in regional lymph nodes, and TSLP and IL-4 in the auricular skin were enhanced by Trichophytin challenge. Interestingly, dectin-1-neutralizing antibody inhibited the promotion of IFN-γ production in C57BL/6 mice, and dectin-1-expressing immune cells had crucial actions in Trichophyton-induced IFN-γ production. CONCLUSION: These results suggest that inflammatory mediators differently regulate Trichophytin-induced contact hypersensitivity on the basis of the status of host immunity.
Subject(s)
Dermatitis, Contact/immunology , Tinea Capitis/immunology , Trichophytin/administration & dosage , Animals , Antibodies, Neutralizing/administration & dosage , Base Sequence , Cytokines/metabolism , Dermatitis, Contact/etiology , Dermatitis, Contact/genetics , Dermatitis, Contact/pathology , Disease Models, Animal , Gene Expression , Humans , Immunity, Innate , Inflammation Mediators/metabolism , Interferon-gamma/biosynthesis , Interferon-gamma/genetics , Interleukin-17/biosynthesis , Interleukin-17/genetics , Interleukin-4/biosynthesis , Interleukin-4/genetics , Lectins, C-Type/antagonists & inhibitors , Lectins, C-Type/genetics , Lectins, C-Type/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , RNA, Messenger/genetics , RNA, Messenger/metabolism , Th1 Cells/immunology , Th2 Cells/immunology , Tinea Capitis/etiology , Tinea Capitis/genetics , Tinea Capitis/pathology , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Trichophyton/immunology , Trichophyton/pathogenicityABSTRACT
To elucidate the mechanisms underlying the self-healing process of experimental dermatophytosis produced in guinea pigs by an occlusive method with Trichophyton mentagrophytes, epidermal proliferative activity was evaluated by the in vivo tritiated thymidine-labeling technique performed at various intervals after the first and second infections. Determination of labeling indices disclosed that an increased epidermal proliferation correlated well with the severity of inflammatory changes, i.e., a peak activity was noted after 10 days in primary infection and at 2 days in reinfection, respectively, and was followed by subsequent spontaneous lesion clearance after 10 days. Application of a heat-killed spore suspension produced inflammatory changes with enhanced epidermopoiesis, similar to those induced by reinoculation of living spores, only in immune animals. The present results indicate that the dermatitic changes occurring in experimental dermatophytosis increase epidermopoiesis which facilitates elimination of the fungus from the stratum corneum and that host immune activity, particularly contact sensitivity to fungal antigen, exerts a crucial role to induce these changes.
