In vitro models of dermatophyte infection to investigate epidermal barrier alterations

Abstract

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, ...

Visualising virulence factors: Trichophyton benhamiaes subtilisins demonstrated in a guinea pig skin ex vivo model

“…These localisations were also observed in skin biopsies of human and animal patients, and after experimental GP infection 5,16,31‐34 . Co‐stainings of sections of infected GPSE with anti‐Dsg1 and anti‐ Trichophyton antibodies substantiate the findings of other authors concerning host tissue invasion, which is described simultaneously intra‐ and intercellularly most likely through concerted mechanical and enzymatic forces 35‐38 …”

Human primary epidermal organoids enable modeling of dermatophyte infections

“…Indeed, our organoids are equipped with epidermal architecture and epidermal cellular microenvironment that can still faithfully reflect the in vivo epidermal responses triggered by T. rubrum. Nevertheless, the absence of immune cells in our organoids results in the inability of the model to recapitulate the complicated immunological responses to the infection exactly as it occurs in vivo, and this is a common defect that also exists in other previously described in vitro skin models, including infection on ALI method-derived epidermis 67 . Additional attempts on introducing the immune cells, such as Langerhans cells, neutrophils, macrophage and different type of lymphocyte, into the cultured organoids to construct immune-competent epidermal models will be helpful to investigate the complex cross-talk between epidermal cells and immune cells, as well as to better understanding of the immune responses of epidermal tissue to dermatophyte infections in the future.…”

Immunopathogenesis of dermatophytoses and factors leading to recalcitrant infections

“…[ 14 ] Consequently, the keratinocytes release antimicrobial peptides (AMP) and pro-inflammatory cytokines, resulting in control and, ultimately, the resolution of infection via the immune system's stimulation. [ 15 ] Further, there may be a role of biofilm formation by making connections between adjacent arthroconidia. [ 16 ]…”