Relevant Animal Models in Dermatophyte Research

Cambier, Ludivine; Heinen, M.; Mignon, Bernard

doi:10.1007/s11046-016-0079-3

Cited by 25 publications

(19 citation statements)

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“…The insufficient knowledge on the global host response against dermatophytosis is notably attributed to the lack of reliable experimental models for dermatophyte infections (Cambier et al, 2017;Shimamura et al, 2012). In our model, the inflammatory signature of clinical signs and microscopic lesions, fungal colonization of keratinized epidermal and follicular structures, and self-healing in WT mice mimic acute superficial tinea in humans from zoophilic dermatophytes such as T. benhamiae (Cambier et al, 2014;Weitzman and Summerbell, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Th1 and Th17 Immune Responses Act Complementarily to Optimally Control Superficial Dermatophytosis

Heinen

Cambier

Antoine

et al. 2019

Journal of Investigative Dermatology

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Dermatophytoses are among the most common fungal infections worldwide but little is known about the immune response in them. By comparing Trichophyton benhamiae acute superficial dermatophytosis in WT and Rag2 mice, we showed that TCR-mediated immunity is critical for fungal clearance and clinical recovery. In WT mice, CD4+ T-cells isolated from the skin-draining lymph nodes exhibit both Th1 and Th17 differentiation during infection, with regard to produced cytokines or mRNA levels of transcription factors. Using IL-17A- and IFN-γ-deficient mice, we showed that IL-17A and IFN-γ are individually dispensable, but together contribute to the optimal resolution of dermatophytosis. Furthermore, we generated and infected IL-17A and IFN-γ double-deficient mice and showed that both fungal clearance and clinical recovery were much lower in these mice than in single-deficient mice, suggestive of the complementary roles of the two cytokines in dermatophytosis resolution. Thus, our data suggest that TCR-mediated immunity is critical for the optimal control of superficial dermatophytosis and that adaptive immunity is polarized to both Th1 and Th17 responses, with the Th17 antifungal response acting on dermatophyte clearance and the Th1 one being involved in both fungal clearance and Th17-inflammation down-modulation.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, the inoculation route in most in vivo models used for studying the immune response against dermatophytes fails to mimic the natural epicutaneous infection or even induce observable skin lesions. This drawback limits the relevance of such animal models, leading to conflicting outcomes (Cambier et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Th1 and Th17 Immune Responses Act Complementarily to Optimally Control Superficial Dermatophytosis

Heinen

Cambier

Antoine

et al. 2019

Journal of Investigative Dermatology

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“…A consistent in vivo model of infection should thus be developed using the natural host. As T. rubrum does not naturally infect non‐human species, the development of an animal model is not fully relevant . Despite those limitations, in vivo models of T. rubrum dermatophytosis using guinea pig or mouse have been reported, but the protocols required multiple application of spores or abrasive treatments to initiate some cutaneous infection.…”

Section: In Vitro Models Of Dermatophytosismentioning

confidence: 99%

“…As T. rubrum does not naturally infect non-human species, the development of an animal model is not fully relevant. [76] Despite those limitations, in vivo models of T. rubrum dermatophytosis using guinea pig [77] or mouse [78,79] have been reported, but the protocols required multiple application of spores or abrasive treatments to initiate some cutaneous infection. Those in vivo models yielded useful information about pathogenic mechanisms, such as F I G U R E 1 Schematic summary of epidermal infection by the anthropophilic dermatophyte Trichophyton rubrum.…”

Section: In Vitro Model S Of Dermatophy Tos Ismentioning

confidence: 99%

In vitro models of dermatophyte infection to investigate epidermal barrier alterations

Faway

Rouvroit

Poumay

2018

Experimental Dermatology

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Dermatophytosis is a superficial fungal infection of keratinized structures caused by specific filamentous fungi named dermatophytes. In humans, the incidence of dermatophytosis is elevated and continuously increasing, rendering it a public health concern. The pathogeny of dermatophytosis remains poorly understood, partly due to the difficulties to set up a relevant model allowing the study of both the invasion of keratinized structures by fungi, and its impact on host tissue architecture and functions. Recently, the development of human cultured skin equivalents has led to some advances. This review aims to summarize current knowledge about dermatophytosis and then focuses on in vitro models to investigate the alterations of the epidermal barrier in response to fungal infection. | DERMATOPHY TOS IS AND DERMATOPHY TE SDermatophytosis is an infection of superficial keratinized epidermal layers, as well as hairs and nails, which is caused by keratinolytic filamentous fungi named dermatophytes.[1] Numerous dermatophyte species are grouped according to their ecological Genome sequencing, especially analysis of the polymorphisms inside the variable rDNA regions known as internal transcribed spacers (ITS), has provided phylogenetic criteria for improved species identification.[4] A revised classification of dermatophytes was proposed, [5][6][7] based on DNA sequences of five different loci, including ITS, on morphology and physiology in culture, and on geo-, zoo-or anthropophilic ecology (Table 1). This review is concerned with anthropophilic and zoophilic dermatophytes frequently responsible for human infections.Dermatophytosis is responsible for 3%-4% of dermatological cases and is the most common fungal infection in humans, with a prevalence estimated around 20%-25%. [8,9] In addition, its prevalence is continuously raising due to increased risk factors such as sport activities, type 2 diabetes, vascular diseases or ageing. Modern mobility further increases the dissemination of anthropophilic dermatophytes that extend in previously poorly affected geographical areas. [10,11] Among the species capable of infecting human skin,Trichophyton rubrum is the most frequently involved, being responsible for 50%-90% of dermatophytoses in humans. [9,12] The annual health expense cost of dermatophytosis is estimated to more than 500 million of US dollars.[13] | Dermatophyte infections induce various clinical picturesThe clinical signs of dermatophytosis result from both the degradation of keratinized tissues caused by fungal processes, as well as from the specific immune response of the infected host.Zoophilic species, probably less adapted to human hosts, generate more severe inflammatory responses than anthropophilic species. [6,14] Usual signs include dryness, desquamation, cracks and erythema of the skin of the feet, scalp or other body locations.Infections in hairless areas and nails, principally due to Trichophyton rubrum and Trichophyton interdigitale, are the most frequent in industrialized countries. Scalp infections, ...

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“…Moreover, silkworms excrete several compounds from the hemolymph into the intestine through a conjugation reaction after metabolism via CYP. 24) Those findings imply that the pharmacokinetics and toxicity of compounds in silkworms are similar to those in mammals. It is assumed that other insects, such as fruit flies, may also have similar systems.…”

Section: Pharmacokinetics and Toxicity Of Com-pounds In Insectsmentioning

confidence: 96%

Facilitating Drug Discovery in Human Disease Models Using Insects

Matsumoto

2020

Biological & Pharmaceutical Bulletin

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Drugs are developed through basic studies and clinical trials. In basic studies, researchers seek drug candidates using in vitro evaluation systems and subsequently examine their effectiveness in animal experiments as in vivo evaluations. Drug candidates identified in basic studies are tested to determine whether they are effective against human diseases in clinical trials. However, most drug candidates identified in in vitro evaluation systems do not show therapeutic effects in animal experiments due to pharmacokinetics and toxicity problems in the in vivo evaluations. This review outlines drug discovery using insect disease models that allow us to perform in vivo screening. Since insects have various advantages as experimental animals such as low cost for rearing and few ethical concerns, researchers can perform large-scale in vivo screening to find drug candidates. Silkworms are insects frequently used for studies of drug efficacy, pharmacokinetics, and toxicity. Based on silkworm research, I describe the benefits of using insect disease models for drug discovery. The use of insect disease models for in vivo screening is expected to facilitate drug discovery.

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Relevant Animal Models in Dermatophyte Research

Cited by 25 publications

References 109 publications

Th1 and Th17 Immune Responses Act Complementarily to Optimally Control Superficial Dermatophytosis

Th1 and Th17 Immune Responses Act Complementarily to Optimally Control Superficial Dermatophytosis

In vitro models of dermatophyte infection to investigate epidermal barrier alterations

Facilitating Drug Discovery in Human Disease Models Using Insects

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