The crosstalk between TLR2 and NOD2 in Aspergillus fumigatus keratitis

Area of Science:

• Immunology
• Ophthalmology
• Microbiology

Background:

• Innate immunity is crucial for fungal keratitis pathogenesis.
• Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs), recognize pathogen-associated molecular patterns (PAMPs) to initiate innate immunity.
• The interplay between TLR2 and NOD2 in Aspergillus fumigatus keratitis remains unclear.

Purpose of the Study:

• To investigate the interaction between TLR2 and NOD2 in human corneal epithelial cells (HCECs) during Aspergillus fumigatus infection.
• To elucidate the roles of TLR2 and NOD2 in the inflammatory response to fungal keratitis.

Main Methods:

• Treatment of immortalized human corneal epithelial cells (HCECs) with Aspergillus fumigatus conidia, muramyl dipeptide (MDP), and zymosan.
• Analysis of NOD2, TLR2, receptor interacting protein 2 (RIP2), nuclear factor κB (NFκB)-p65, inhibitor of NFκB (IκB)-α, and inflammatory cytokine (IL-6, IL-8, TNF-α) expression.
• Utilized small interfering RNA (siRNA) for NOD2 knockdown.

Main Results:

• A. fumigatus conidia increased NOD2 and TLR2 expression in HCECs.
• NOD2 activation by MDP upregulated RIP2, NFκB-p65, IκB-α, and inflammatory cytokines.
• Zymosan (TLR2 agonist) promoted NOD2 and RIP2 expression in a TLR2-dependent manner, but pretreatment with zymosan decreased NOD2, RIP2, and MDP-induced cytokine secretion.
• NOD2 knockdown reduced inflammatory cytokine release induced by A. fumigatus conidia.

Conclusions:

• A complex, bidirectional interaction exists between TLR2 and NOD2 in HCECs during A. fumigatus infection.
• TLR2 signaling partially mediates the increased expression of NOD2 and RIP2 induced by A. fumigatus conidia.
• These findings highlight the intricate immune mechanisms involved in fungal keratitis.