Skin Immunity to Dermatophytes: From Experimental Infection Models to Human Disease.

Verónica L Burstein,Laura S Chiapello,Laura Cervi,Cristian J Mena,Ignacio Beccacece,Lorena Guasconi

doi:10.3389/fimmu.2020.605644

Abstract

Dermatophytoses (ringworms) are among the most frequent skin infections and are a highly prevalent cause of human disease worldwide. Despite the incidence of these superficial mycoses in healthy people and the compelling evidence on chronic and deep infections in immunocompromised individuals, the mechanisms controlling dermatophyte invasion in the skin are scarcely known. In the last years, the association between certain primary immunodeficiencies and the susceptibility to severe dermatophytosis as well as the evidence provided by novel experimental models mimicking human disease have significantly contributed to deciphering the basic immunological mechanisms against dermatophytes. In this review, we outline the current knowledge on fungal virulence factors involved in the pathogenesis of dermatophytoses and recent evidence from human infections and experimental models that shed light on the cells and molecules involved in the antifungal cutaneous immune response. The latest highlights emphasize the contribution of C-type lectin receptors signaling and the cellular immune response mediated by IL-17 and IFN-γ in the anti-dermatophytic defense and skin inflammation control.

Highlights

The skin is the most extensive organ of the body, is an ecological niche for microbiota and the first barrier against aggression from environmental noxa and pathogenic microorganisms
This study showed that dermatophytes can modulate the host innate immune response by producing extracellular vesicles (EVs) loaded with still undefined dermatophyte virulence factors that interact with Toll-like Receptors (TLR)
In line with the experimental data observed in the M. canis mouse model, patients with mutations that lead to the gain of function in the transcription factor STAT1 (STAT1 GOF), that promote type I and type II IFN genes transcription, have reduced type 17 immunity and are susceptible to chronic mucocutaneous candidiasis (CMC) and dermatophytosis [96, 97, 114,115,116,117]

Summary

Introduction

The skin is the most extensive organ of the body, is an ecological niche for microbiota and the first barrier against aggression from environmental noxa and pathogenic microorganisms. CXCL8 is a member of the CXCL chemokine family primarily involved in neutrophil recruitment and activation in response to tissue damage or infection [59] and can be directly induced in human keratinocytes by dermatophytes [53, 60].

Results

Conclusion