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Tissue remodeling by an opportunistic pathogen triggers allergic inflammation

  • Karen Agaronyan
  • , Lokesh Sharma
  • , Bharat Vaidyanathan
  • , Keith Glenn
  • , Shuang Yu
  • , Charles Annicelli
  • , Talia D. Wiggen
  • , Mitchell R. Penningroth
  • , Ryan C. Hunter
  • , Charles S. Dela Cruz
  • , Ruslan Medzhitov
  • Yale University
  • University of Minnesota Twin Cities

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish
Pages (from-to)895-911.e10
JournalImmunity
Volume55
Issue number5
DOIs
StatePublished - May 10 2022

Keywords

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

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