Pathogenic fungus Microsporum canis activates the NLRP3 inflammasome.

Microsporum canis is a pathogenic fungus with worldwide distribution that causes tinea capitis in animals and humans. M. canis also causes invasive infection in immunocompromised patients. To defy pathogenic fungal infection, the host innate immune system is the first line of defense. As an important arm of innate immunity, the inflammasomes are intracellular multiprotein complexes that control the activation of caspase-1, which cleaves proinflammatory cytokine pro-interleukin-1ß (IL-1ß) into its mature form. To determine whether the inflammasome is involved in the host defense against M. canis infection, we challenged human monocytic THP-1 cells and mouse dendritic cells with a clinical strain of M. canis isolated from patients with tinea capitis. We found that M. canis infection triggered rapid secretion of IL-1ß from both THP-1 cells and mouse dendritic cells. Moreover, by using gene-specific shRNA and competitive inhibitors, we determined that M. canis-induced IL-1ß secretion was dependent on NLRP3. The pathways proposed for NLRP3 inflammasome activation, namely, cathepsin B activity, K(+) efflux, and reactive oxygen species production, were all required for the inflammasome activation triggered by M. canis. Meanwhile, Syk, Dectin-1, and Card9 were found to be involved in M. canis-induced IL-1ß secretion via regulation of pro-IL-1ß transcription. More importantly, our data revealed that M. canis-induced production of IL-1ß was dependent on the NLRP3 inflammasome in vivo. Together, this study unveils that the NLRP3 inflammasome exerts a critical role in host innate immune responses against M. canis infection, and our data suggest that diseases that result from M. canis infection might be controlled by regulating the activation of inflammasomes.

Inflammatory Tinea capitis: a 12-year study and a review of the literature.

Inflammatory Tinea capitis (TC) is a rare form of TC. The aim of this study was to review epidemiological, clinical and mycological profile of inflammatory TC. We present a retrospective study (1999-2010), enrolled all the cases of inflammatory TC observed at a referral hospital in the northern Tunisia. One hundred and twenty-one patients with inflammatory TC, 83 male patients (68.6%) and 38 female patients (31.4%) were enrolled. The mean age was about 8 years. A majority of TC (71.9%) were in patients lesser than 10 years of age. Positive family history and contact with animals were noted in seven and 35 cases respectively. Direct examination was positive in 110 cases (59 ectothrix, 51 endothrix) and positive cultures were obtained in 105 patients (49 Trichophyton violaceum, 31 Microsporum canis, 13 Trichophyton interdigitale complex, 12 Trichophyton verrucosum). Systemic treatment was carried out in 115 patients with griseofulvin, in one with terbinafine. A complete recovery was noted in 88 cases; and persistent alopecia in 28 cases. The inflammatory TC is rare, but more common in rural families. The disease mostly affected male genders (68.6%) and T. violaceum remains the common pathogen of inflammatory TC in northern Tunisia.

Tinea capitis mimicking cicatricial alopecia: what host and dermatophyte factors lead to this unusual clinical presentation?

Tinea capitis is the most common dermatophyte infection in children. The clinical presentation varies from subtle asymptomatic scaling to inflammatory suppurative nodules and draining tracks. Both chronic and acute inflammatory infections may damage the hair follicle leading to secondary cicatricial alopecia. In rare instances, the initial presentation can mimic a primary cicatricial alopecia. We present three cases of tinea capitis in children masquerading as cicatricial alopecia and discuss the possible host immune and fungal antigenic factors that may influence the course of disease and its clinical presentation. An understanding of the clinical morphology of tinea capitis in the context of both host and fungal factors may improve treatment strategies and direct future paradigms of therapy.

Trichophyton tonsurans-induced kerion celsi with decreased defensin expression and paradoxically increased interleukin-17A production.

We report a case of kerion celsi due to Trichophyton tonsurans. An 18-year-old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human ß-defensin 2 (HBD-2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)-17A generally induces HBD-2 production by epidermal keratinocytes, we also immunohistochemically investigated IL-17A expression. Unexpectedly, many IL-17A-bearing cells were found around destructed hair follicles, indicating that IL-17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL-17A-upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL-17A may cause tissue damage and resultant scar.

Atypical Microsporum canis variant in an immunosuppressed child.

A 10-year old boy with X-chromosomal adrenoleukodystrophy presented with scaly patches on the scalp and diffuse effluvium. He was on immunosuppressive therapy because of a chronic graft-versus-host-reaction after allogenic bone marrow transplantation. At home he had been in contact with cats, rabbits and guinea pigs. Through Wood light and KOH examination, we confirmed the diagnosis of tinea capitis and started antimycotic therapy. The morphology of the culture first suggested Epidermophyton floccosum, Trichophyton mentagrophytes var. nodulare or Trichophyton tonsurans as possible causes for this infection. Further studies, however, revealed an atypical form of Microsporum canis infection.

Pseudomycetoma for microsporum canis: report of a case diagnosed by fine needle aspiration biopsy.

BACKGROUND: Fine needle aspiration biopsy (FNAB) of the skin is useful in subcutaneous lesions. Dermatophytes are almost exclusively superficial cutaneous mycoses and constitute 70-80% of all mycoses and 5% of dermatologic consultations. Inflammatory and invasive forms, as well as infections that remain in chronic forms or persist in spite of treatment, are more frequent in immunocompromised individuals. The clinicalpresentations of these invasive cases are dermatopbytic granulomas (granuloma of Wilson-Majocchi and pseudomycetoma) or Hadida's disease. CASE: A 17-year-old male with an 8-year history of tinea capitis and multiple kerion lesions in the occipital region, left foot and right elbow resistant to conventional treatment was diagnosed by KOH tests and cultures as Microsporum canis. Two months before consultation he noticed the slow growth of a subcutaneous nodule in the base of the neck. FNAB of the neck nodule was performed. The diagnosis of pseudomycetoma by Microsporum canis was made. CONCLUSION: We report a case of pseudomycetoma caused by Microsporum canis, with the diagnosis made by FNAB. This case appears to be the first one diagnosed by this method in a human.

Trichophytin reactions in children with tinea capitis.

Of 52 patients with proved Trichophyton tonsurans infection of the scalp, 16 had an inflammatory reaction to this infection (kerion), while the rest had only slight scaling and broken hairs (black dot ring-worm). Each patient was tested with trichophytin antigen to determine whether cell-mediated immunity (CMI) was responsible for the differences in these different clinical presentations. Fifteen of 16 with kerion had a 48-hour reaction greater than 10 mm, while none of the 36 with noninflammatory (black dot) tinea capitis had a similar response. This suggests that the patient's immune response (CMI) may be responsible for kerion infections of the scalp and that therapy could be directed initially toward suppressing this reaction.

Immunohistochemical analysis of the infiltrated cells in tinea capitis patients.

Tinea capitis is a fungal infection of the skin and the hair with involvement of the hair shaft and the pilosebaceous unit. It may be the most common of all cutaneous mycoses in children. Tinea capitis can be inflammatory or noninflammatory. It is thought that humoral and cell-mediated immunities play a role in the formation of the clinical types of the disease. We studied twelve patients with acute inflammatory disease, four patients with chronic non-inflammatory disease, and one patient with a black-dot variant of tinea capitis. The composition of inflammatory infiltrates present in lesional skin was analyzed by antibodies to T cells (CD3) and B cells (CD20). Anti-CD3 revealed large numbers of T cells in twelve patients with acute, inflammatory dermatophytosis, whereas anti-CD20 revealed marked infiltrates of both B and T cells in all patients with chronic, non-inflammatory dermatophytosis. As a result, we thought that cell-mediated immunity might play a role in the acute, inflammatory type of tinea capitis and that humoral immunity might do so in the chronic, non-inflammatory type of tinea capitis.

[Microsporic tinea of the scalp in adults]. / Tiña microspórica de cuero cabelludo en adultos.

Five cases of "tinea capitis" by Microsporum canis in adult were studied. Cellular immunological tests were performed on four of them and the results were according to clinical forms. The hormonal studies in these patients were normal to their ages. Three of them were old women. Two cases were atypical difficult to diagnose. For this reason the authors suggest to perform mycological studies in every scalp affections were it is impossible to do a clinical and evolutive positive diagnosis. All the patients healed with local and systemie antimycotical treatment.

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-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.

An immunological study of a case of tinea capitis in an adult.

We evaluated the immunological aspects of a case of tinea capitis in an adult. Tests revealed alteration of the T4/T8 lymphocyte ratio (T4 increase and T8 decrease) and a decrease in polymorphonuclear leukocyte activity.

Dermatophytosis of the scalp: incidence, immune response, and epidemiology.

Tinea capitis remains a common infection among the pediatric population of North America. The 'gray patch' Microsporum audouinii infections of the 1950's have been supplanted by the 'black dot' ringworm of Trichophyton tonsurans. The clinical presentation of T. tonsurans infection is quite variable and may be related to specific host T-lymphocyte response. This dermatophytosis is most frequently incurred from contact with an infected child either directly or via a variety of fomites. Current studies indicate that an asymptomatic adult carrier state may also exist which could contribute to the morbidity of this mycosis.