IL-17-Mediated Immunity Controls Skin Infection and T Helper 1 Response during Experimental Microsporum...

Area of Science:

• Immunology
• Dermatology
• Mycology

Background:

• Superficial mycoses are common globally, yet the immune response in dermatophytosis remains poorly understood.
• Dermatophytosis, fungal infections of the skin, hair, and nails, affects a significant portion of the human population worldwide.

Purpose of the Study:

• To investigate the immune response in a mouse model of superficial skin infection caused by Microsporum canis.
• To elucidate the role of Interleukin-17 (IL-17) signaling in controlling dermatophytosis and modulating the host's immune response.

Main Methods:

• Development of a Microsporum canis superficial skin infection model in C57BL/6 mice.
• Utilizing IL-17RA- or IL-17A/F-deficient mice to assess the impact of IL-17 pathway deficiency.
• Analysis of immune responses, including neutrophil recruitment, fungal colonization, and T helper cell polarization (Th1 and Th17).

Main Results:

• The mouse model successfully mimicked mild human inflammatory dermatophytosis with epidermal fungal invasion and neutrophil recruitment.
• Absence of functional IL-17 signaling led to extensive M. canis colonization, exaggerated skin inflammation, and a shift towards a T helper type 1 (IFN-γ-mediated) response.
• IL-17 signaling did not influence neutrophil influx or deeper tissue fungal invasion.
• Skin langerin-expressing cells were identified as contributors to the antifungal T helper type 17 response in vivo.

Conclusions:

• IL-17 cytokines play a dual role in dermatophytosis: controlling superficial fungal infection and down-modulating the T helper type 1 antifungal response.
• The findings underscore the critical role of the IL-17 pathway in maintaining immune balance during superficial fungal skin infections.