Host immune responses in dermatophytes infection.

Dermatophytosis is a skin infection caused by keratinophilic, filamentous fungi. These are highly prevalent, common mycoses, affecting approximately 20% of the population. These fungi invade the stratum corneum, and other keratinised tissues, like nails and hair, where they grow by secreting enzymes and degrading keratin to obtain nutrients. Clinical presentation is variable and may depend on many factors, such as the infection site, the host's immunity and the dermatophyte's virulence. Generally, patients with acute superficial dermatophytosis mount cell-mediated immune responses. However, those suffering from chronic or recurrent infections are unable to develop this response, for reasons yet unknown. Several reports have described severe and occasionally life-threatening invasive diseases (deep dermatophytosis) associated with genetic mutations in the innate immunity-associated molecule CARD9, displaying the need to better understand its immune response. These dermatoses have substantial clinical consequences, producing chronic and difficult to treat skin lesions. They also lead to a decline in the patient's quality of life and impact their self-esteem. This review summarises findings on the immune response against dermatophytes.

The Dermatophyte Trichophyton rubrum Induces Neutrophil Extracellular Traps Release by Human Neutrophils.

Neutrophils are the first leukocytes recruited to the site of infection and are thought to be responsible for fungal elimination from the skin such as dermatophytes. Neutrophils are able to secrete reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) that can kill different fungi, including Aspergillus, spp., Candida albicans, and Phialophora verrucosa. However, NET production in response to Trichophyton rubrum, the main etiologic agent of dermatophytosis, has yet to be studied. We demonstrated that human neutrophils produce NETs against different morphotypes of T. rubrum in a dose-dependent manner and NET formation is dependent on ROS production. In addition, ROS production by human neutrophils in response to T. rubrum is dependent on NADPH oxidase, but not on fungal viability. NETs mediated killing of T. rubrum. Collectively, these results demonstrate that T. rubrum was able to trigger the production of NETs, suggesting that these extracellular structures may represent an important innate immune effector mechanism controlling physiological response to T. rubrum infection.

Trichophyton rubrum Elicits Phagocytic and Pro-inflammatory Responses in Human Monocytes Through Toll-Like Receptor 2.

Dermatophytosis is a superficial fungal infection mostly restricted to keratinized tissues such as skin, hair, and nails but with potential to cause invasive or even systemic disease in immunocompromised patients. Trichophyton rubrum is the main etiologic agent, accounting for approximately 80% of the cases. Mononuclear phagocytes respond to pathogens through phagocytosis followed by production of several antimicrobial molecules, such as reactive oxygen and nitrogen species, and failure in doing so may contribute to development of chronic fungal infections. Toll-like receptors (TLRs) located on the surface of phagocytic cells bind either directly to target particles or through opsonizing ligands and trigger an actin-mediated ingestion. Even though the mechanisms involved in TLR-mediated cytokine responses are well established, the contribution of TLR in the recognition of T. rubrum by adherent monocytes remains unclear. Here, we report that phagocytosis of T. rubrum conidia by adherent monocytes is mediated by TLR2. Blockade of TLR2 by neutralizing antibodies impaired the fungicidal activity of monocytes as well their secretion of tumor necrosis factor (TNF)-α, but neither nitric oxide (NO) production nor interleukin (IL)-10 secretion was disturbed. So far, our data suggest that TLR2 is required for efficient conidial phagocytosis, and the absence of TLR2 signaling in human monocytes may impair the subsequent inflammatory response. These findings expand our understanding of phagocyte modulation by this important fungal pathogen and may represent a potential target for interventions aiming at enhancing antifungal immune responses.