Immunopathogenesis of dermatophytoses and factors leading to recalcitrant infections

Abstract

The pathogenesis of dermatophytic infections involves the interplay of three major factors: the dermatophyte, the inherent host defense, and the adaptive host immune response. The fungal virulence factors determine the adhesion and invasion of the skin while the immune response depends on an interaction of the pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMP) with pattern recognition receptors (PRRs) of the host, which lead to a differential Th (T helper) 1, Th2, Th17, and Treg response. While anthropophilic dermatophytes Trichophyton rubrum and now increasingly by T. interdigitale subvert the immune response via mannans, zoophilic species are eliminated due to a brisk immune response. Notably, delayed-type hypersensitivity (Th1) response of T lymphocytes causes the elimination of fungal infection, while chronic disease caused by anthropophilic species corresponds to toll-like receptor 2 mediated IL (interleukin)-10 release and generation of T-regulatory cells with immunosuppressive potential. Major steps that determine the ultimate clinical course and chronicity include genetic susceptibility factors, impaired epidermal and immunological barriers, variations in the composition of sebum and sweat, carbon dioxide tension, skin pH, and topical steroid abuse. It is important to understand these multifarious aspects to surmount the problem of recalcitrant dermatophytosis when the disorder fails conventional therapeutic agents.

Trichophyton indotineae—An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide—A Multidimensional Perspective

“…At present, there are no unique features of the immune response to T. indotineae . The immunological response is similar to that occurring with other dermatophytes such as T. rubrum [ 61 ].…”

Dermatophytoses Severity Score – A novel point‐of‐care scoring tool to assess the severity of dermatophytosis

“…It is primarily devised to be an examination tool, to succinctly describe the severity of dermatophytosis across the treatment course, in each clinical encounter. This tool which accounts for physician‐rated clinical severity is best used in conjunction with patient's measure of quality of life, to comprehensively describe severity 21 …”

Pathogenesis, Immunology and Management of Dermatophytosis

“…Under favorable conditions, after inoculation into the host skin, epidermal adhesion occurs within an hour, mediated by adhesins present on the fungal cell wall [15,16]. This is followed by penetration mediated by proteases, serine subtilisin and fungalysin, which digests the keratin and also acts as a potent immunogenic stimulus [15].…”

“…There are various host defense mechanisms that avoid establishment of infection, including composition (physical or chemical) of skin, exposure to UV light, lack of humidity, temperature, etc. [16,18].…”