Tissue remodeling by an opportunistic pathogen triggers allergic inflammation

Immunity. 2022 May 10;55(5):895-911.e10. doi: 10.1016/j.immuni.2022.04.001. Epub 2022 Apr 27.

Abstract

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.

Keywords: LasB; P. aeruginosa; allergic inflammation; amphiregulin; immune deviation; lung; mucin; opportunistic pathogen; type 2 immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins
  • Humans
  • Inflammation
  • Mucins
  • Pseudomonas Infections*
  • Pseudomonas aeruginosa*

Substances

  • Bacterial Proteins
  • Mucins