Akiko Nishibu

Analysis of Trichophyton antigen-induced contact hypersensitivity in mouse

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-1β, 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.

Glycyrrhetinic acid inhibits contact hypersensitivity induced by trichophytin via dectin-1

Trichophyton infection is highly prevalent and tends to be recurrent. Therefore, it is important to develop new therapeutic agents. Previously, we established a mouse model of Trichophyton‐induced contact hypersensitivity (CHS) and demonstrated that dectin‐1 was involved in inflammation induced by trichophytin, the Trichophyton antigen. Here, we used that model to investigate glycyrrhetinic acid (GA) from plants of the genus Glycyrrhiza as a potential anti‐inflammatory agent against superficial mycoses. GA suppressed swelling and the expression of inflammatory cytokines, including macrophage inflammatory protein (MIP)‐2, interleukin (IL)‐6, tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ mRNA. Anti‐MIP‐2 antibody suppressed trichophytin‐induced inflammation, and antidectin‐1 antibody suppressed zymosan‐induced MIP‐2 production in keratinocyte cells. These results suggest that MIP‐2 is produced by dectin‐1 activation and is involved in inflammation associated with CHS to trichophytin. GA also suppressed zymosan‐induced MIP‐2 and interleukin (IL)‐8, production in mouse and human macrophages and keratinocytes. Furthermore, GA suppressed the phosphorylation of spleen tyrosine kinase (Syk) and inhibitor of nuclear factor‐kappa B (IκBα) and the degradation of IκBα in zymosan‐simulated RAW264.7 cells. The results of this study suggest that GA suppresses inflammation induced by trichophytin, partly by the downregulation of Syk phosphorylation.

Polyclonality of Trichophyton rubrum Isolates in aDermatophytosis Patient with Multiple Lesions.

We cultured 15 isolates of Trichophyton rubrum and one isolate of Trichophyton mentagrophytes from an 82-year-old male tinea patient with multiple lesions. To determine whether feet lesions were the source of dermatophytes of other tinea lesions, we extracted total cellular DNA from the T. rubrum isolates（13 from feet, two from right waist and buttock）. PCR targeting the non-transcribed spacer（NTS）region of ribosomal RNA gene was performed. Molecular polymorphisms were detected by length variation of amplicons.Four molecular types were found among the 15 isolates. The predominant type, which we previously named Type III, comprised seven isolates cultured from both feet and from left waist and buttock. This was followed by Type VI, five isolates; Type V, two isolates; and Type IV, one isolate. Apart from type III, which was cultured from both feet, isolates were cultured from one foot only. The patient was successfully treated for all types with a six-month course of oral terbinafine and topical luliconazole. The molecular typing supported the notion that tinea pedis was the source of tinea corporis in the patient.

Case of phaeohyphomycosis producing sporotrichoid lesions

A 90‐year‐old Japanese woman, taking prednisolone (5–10 mg/day) for polyarthritis, presented to our hospital with multiple subcutaneous lesions on her left arm in 2009. Her history included excision of a phaeomycotic cyst on the left middle finger in 2007. There were three subcutaneous nodules approximately 15 mm in diameter around her left wrist and a large soft cystic lesion measuring 80 mm × 60 mm on her left elbow. A granuloma with neutrophilic infiltration was detected in the deep dermis of a biopsy specimen. Chains composed of round brown cells and short pseudomycelia were found in the granuloma. Fungal cultures from the samples confirmed Exophiala sp. to be the causative agent. Treatment with terbinafine and local hyperthermia seemed effective as all the lesions tended to subside. However, the patient died due to pneumonia approximately 1 month after commencement of therapy.

Itching in a trichophytin contact dermatitis mouse model and the antipruritic effect of antifungal agents

Tinea is an infectious disease by dermatophytes, of which Trichophyton species accounts for the overwhelming majority of case. Tinea often causes itching with inflammation. In terms of pruritus by fungal infection, however, tinea has not been investigated sufficiently to date.

Case of inflammatory tinea corporis affecting the dorsal surface of the thumb in a nail salon technician

Dear Editor, Nail salons are rapidly expanding in the cosmetic field. Accordingly, there are growing concerns among nail salon technicians about potential health issues such as respiratory and musculoskeletal problems. Herein, we report the first case of inflammatory tinea corporis affecting the dorsal surface of the thumb in a nail salon technician. A 23-year-old woman visited our hospital complaining of a painful eruption, which had appeared 2 weeks earlier, on the right thumb. She had been treated with topical corticosteroid ointment for 6 days, followed by oral ofloxacin alone for 4 days at another clinic without improvement. She was working as a nail salon technician and engaged in pedicures without using protective gloves. Otherwise, she had an unremarkable medical history, no pets and no family history of dermatophytosis. Clinical examination revealed a well-circumscribed erythema with peripheral pustules on the dorsal surface of the right thumb (Fig. 1a). There was no remarkable lesion on the palms, feet or nails. Skin cultures were negative for bacterial growth.