The Fungal Secretory Peptide Micasin Induces Itch by Activating MRGPRX1/C11/A1 on Peripheral Neurons

Area of Science:

• Dermatology
• Neuroscience
• Molecular Biology

Background:

• Pruritus (itching) is a primary symptom of dermatophytosis, a fungal infection.
• Microsporium canis is a common cause of dermatophytosis, but the itch-inducing agents and mechanisms are unclear.

Purpose of the Study:

• To identify the specific agents secreted by Microsporium canis that cause pruritus.
• To elucidate the molecular mechanisms underlying M. canis-induced itch.

Main Methods:

• Mice were used to test the itch-inducing effects of M. canis secretions.
• The fungal peptide micasin was identified and its role in activating neurons was investigated.
• Knockout and antagonistic experiments were performed on specific receptors (MRGPRX1/C11/A1 and MRGPRX2/b2).
• Structural analysis of MRGPRX1 was conducted using chimeras and variants.

Main Results:

• M. canis secretions dose-dependently induced itch in mice.
• The peptide micasin was identified as a key pruritogenic agent, activating dorsal root ganglia neurons.
• Micasin-triggered itch involved the activation of MRGPRX1/C11/A1, not MRGPRX2/b2.
• Specific domains and residues of MRGPRX1 were found crucial for micasin activation.

Conclusions:

• Micasin is a novel pruritogenic peptide from M. canis that activates nonhistaminergic itch pathways.
• MRGPRX1 is the primary receptor mediating micasin-induced pruritus.
• This research identifies potential therapeutic targets for treating fungal infection-related itching.