Mucosal sensitization to German cockroach involves protease-activated receptor-2.

Area of Science:

• Immunology
• Allergology
• Respiratory Medicine

Background:

• Allergic asthma prevalence is increasing globally.
• Allergens often possess protease activity, activating protease-activated receptor-2 (PAR-2).
• The role of PAR-2 in allergic airway inflammation from real-world allergens remains unclear.

Purpose of the Study:

• To investigate the role of PAR-2 in allergic airway inflammation induced by German cockroach (GC) frass.
• To determine if allergen protease activity and route of exposure influence PAR-2 mediated inflammation.

Main Methods:

• Mice (wild type and PAR-2-deficient) were sensitized to GC frass via mucosal (intratracheal) or systemic (intraperitoneal) routes.
• Protease-depleted GC frass was used to assess the role of protease activity.
• Airway inflammation markers (cytokines, IgE, cellular infiltration, mucin) and hyperresponsiveness were measured.

Main Results:

• Systemic sensitization to GC frass induced airway inflammation and hyperresponsiveness in wild-type mice, with no difference in PAR-2-deficient mice.
• Mucosal sensitization to GC frass led to significantly reduced airway hyperresponsiveness, Th2/Th17 cytokine release, IgE, and cellular infiltration in PAR-2-deficient mice compared to wild-type.
• Protease depletion from GC frass did not affect inflammation when administered systemically.

Conclusions:

• Allergen-derived proteases in GC frass elicit allergic airway inflammation through PAR-2, but exclusively upon mucosal exposure.
• Resident airway cells are crucial in initiating allergic airway disease.
• Allergen-derived proteases represent promising therapeutic targets for allergic asthma.