Innate signals from Nod2 block respiratory tolerance and program T(H)2-driven allergic inflammation

Area of Science:

• Immunology
• Pulmonology
• Microbiology

Background:

• Airway tolerance is crucial for lung health against allergens.
• Factors disrupting tolerance and causing allergic asthma are not fully understood.

Purpose of the Study:

• To determine if bacterial pattern recognition in the lung induces allergic reactions.
• To elucidate mechanisms by which triggers block natural airway tolerance.

Main Methods:

• Intranasal administration of Nod1 and Nod2 ligands with antigen.
• Analysis of modulation of airway tolerance by these ligands.

Main Results:

• Nod2 ligand induced innate cytokines (TSLP, IL-25) and OX40 ligand.
• These molecules blocked regulatory T cell generation and promoted TH2 cells.
• This imbalance led to susceptibility to eosinophilic airway inflammation.

Conclusions:

• Nod-like receptors represent a novel pathway linking innate and adaptive immunity.
• This pathway adversely affects immune responses, leading to allergic disease and asthma.