MCPIP1 alleviates inflammatory response through inducing autophagy in Aspergillus fumigatus keratitis

Area of Science:

• Ophthalmology
• Immunology
• Microbiology

Background:

• Fungal keratitis (FK) is a severe corneal infection.
• Monocyte chemoattractant protein-induced protein 1 (MCPIP1) is known to regulate inflammatory responses.
• The role of MCPIP1 in Aspergillus fumigatus (A. fumigatus) keratitis was previously unknown.

Purpose of the Study:

• To investigate the function of MCPIP1 in A. fumigatus-induced fungal keratitis.
• To determine the mechanism by which MCPIP1 affects inflammatory responses and autophagy in corneal cells.

Main Methods:

• Studied MCPIP1 expression in human corneal epithelial cells (HCECs) and mouse corneas following A. fumigatus infection.
• Manipulated MCPIP1 levels (overexpression and knockdown) to assess its impact on inflammatory cytokine production.
• Investigated the effect of MCPIP1 on autophagy flux and mTOR signaling pathway.
• Utilized chloroquine to inhibit autophagy and evaluate its interaction with MCPIP1's anti-inflammatory effects.
• Assessed the therapeutic potential of MCPIP1 in an FK mouse model.

Main Results:

• A. fumigatus infection increased MCPIP1 expression in HCECs and mouse corneas.
• MCPIP1 overexpression reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), while MCPIP1 knockdown increased them.
• MCPIP1 promoted autophagy flux by inhibiting the mTOR signaling pathway.
• Inhibition of autophagy reversed the anti-inflammatory effects of MCPIP1.
• MCPIP1 treatment alleviated keratitis severity and reduced inflammation in vivo by activating autophagy.

Conclusions:

• MCPIP1 plays a protective role in A. fumigatus keratitis by suppressing inflammation.
• MCPIP1 exerts its anti-inflammatory effects through the induction of mTOR-mediated autophagy.
• MCPIP1 protein shows potential as a therapeutic agent for clinical treatment of fungal keratitis.