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

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.

State-of-the-Art Dermatophyte Infections: Epidemiology Aspects, Pathophysiology, and Resistance Mechanisms

“…During infection, dermatophytes trigger the release of cytokines and chemokines that contribute to the inflammatory response in the skin. While zoophilic species induce a broad range of immunological mediators, anthropophilic dermatophytes induce lower levels of these molecules, corroborating the histological and clinical manifestations observed in dermatophytosis [ 27 ].…”

Apiaceae Essential Oils: Boosters of Terbinafine Activity against Dermatophytes and Potent Anti-Inflammatory Effectors

“…Human neutrophils are primarily involved in the host defense mechanism against T. rubrum, as both clinical setups and animal model experiments revealed a dense infiltration of neutrophils in infected areas [67]. Following recruitment from the bloodstream, neutrophils' activation and responses to a fungi attack include: phagocytosis, an oxidative burst by reactive oxygen species production, the secretion of proteases, the release of extracellular traps, the secretion of pro-inflammatory cytokines (e.g., IL-1β, IL-6, IL-8, and TNF-α), chemokines, and growth factors [1,68,69]. However, the prolonged activation of neutrophils hinders the resolution of infection, sustaining a chronic inflammation which in turn can contribute to colonization of the neighboring host tissue [70].…”

“…Dermatophytes are filamentous fungi with a high affinity for the keratinized tissue of the skin, nails, and hair, causing superficial infections with different degrees of inflammation known as dermatophytoses [1,2]. According to data from the World Health Organization, dermatophytosis has become a public health issue, affecting up to a quarter of the global population; its incidence is influenced by different factors, e.g., age, sex, the season, socioeconomic status, and geographical region [3].…”

In vitro antidermatophytic activity of bioactive compounds from selected medicinal plants

“…Dermatophytoses are characterized by superficial invasion by fungal hyphae in the skin, hair, and nails causing subacute or chronic infections (Burstein et al 2020 ). Although dermatophyte infections are restricted to areas of the epidermis, they can be invasive and cause serious widespread infections in immunocompromised patients (Trottier et al 2020 ).…”