Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2

Area of Science:

• Immunology
• Environmental Microbiology
• Allergology

Background:

• Acanthamoeba is a ubiquitous free-living amoeba found in the environment.
• It possesses potent proteases capable of inducing allergic airway inflammation.
• The aeroallergenicity of Acanthamoeba has not been previously documented.

Purpose of the Study:

• To investigate the potential of Acanthamoeba as an aeroallergen.
• To elucidate the mechanisms by which Acanthamoeba may induce allergic airway inflammation.
• To assess the relevance of Acanthamoeba in human allergic airway diseases.

Main Methods:

• Mice were intranasally inoculated with Acanthamoeba trophozoites or excretory-secretory (ES) proteins.
• Immune responses, chemokine gene expression, and T cell differentiation were evaluated.
• Protease activity was assessed using phenyl-methane-sulfonyl fluoride (PMSF).
• Protease-activated receptor 2 knockout mice were used to assess the role of this receptor.

Main Results:

• Acanthamoeba exposure induced allergic airway inflammation and Th2 immune responses in mice.
• ES proteins exhibited protease activity, activating chemokine genes (CCL11, CCL17, CCL22, TSLP, IL-25) in lung epithelial cells.
• PMSF inhibited ES protein activity.
• ES proteins stimulated dendritic cells and promoted differentiation of naive T cells into IL-4-secreting cells.
• In protease-activated receptor 2 knockout mice, inflammation and Th2 responses were reduced.
• Asthma patients showed higher Acanthamoeba-specific IgE levels than healthy controls.
• Acanthamoeba antigen was detected in house dust.

Conclusions:

• Acanthamoeba proteases act as allergens, eliciting allergic airway symptoms in a mouse model.
• Acanthamoeba may be a contributing factor to human allergic airway diseases.
• The findings highlight Acanthamoeba as a potential environmental allergen.