Tissue remodeling by an opportunistic pathogen triggers allergic inflammation

Highlights

• P. aeruginosa toxin LasB activates amphiregulin-EGFR axis to induce tissue repair genes

• P. aeruginosa use amphiregulin to promote bacterial colonization

• P. aeruginosa can grow on purified mucin and human sputum samples

• LasB and P. aeruginosa can serve as adjuvants for allergic responses

Summary

Different effector arms of the immune system are optimized to protect from different classes of pathogens. In some cases, pathogens manipulate the host immune system to promote the wrong type of effector response—a phenomenon known as immune deviation. Typically, immune deviation helps pathogens to avoid destructive immune responses. Here, we report on a type of immune deviation whereby an opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa), induces the type 2 immune response resulting in mucin production that is used as an energy source by the pathogen. Specifically, P. aeruginosa-secreted toxin, LasB, processed and activated epithelial amphiregulin to induce type 2 inflammation and mucin production. This “niche remodeling” by P. aeruginosa promoted colonization and, as a by-product, allergic sensitization. Our study thus reveals a type of bacterial immune deviation by increasing nutrient supply. It also uncovers a mechanism of allergic sensitization by a bacterial virulence factor.