The Helicobacter pylori virulence effector CagA abrogates human β-defensin 3 expression via inactivation of EGFR signaling

Cell Host Microbe. 2012 Jun 14;11(6):576-86. doi: 10.1016/j.chom.2012.04.013.


Antimicrobial peptides are constituents of the first-line innate mucosal defense system that acts as a barrier to establishment of infection. The highly successful human gastric pathogen, Helicobacter pylori, is able to persistently colonize its host despite inducing expression of several antimicrobial peptides, including human β-defensin 3 (hBD3). We find that hBD3 is highly active against H. pylori in vitro and is rapidly induced during early infection via EGFR-dependent activation of MAP kinase and JAK/STAT signaling. However, during prolonged infection, hBD3 was subsequently downregulated by the H. pylori virulence determinant CagA. Upon translocation into host cells, CagA activated the cellular tyrosine phosphatase, SHP-2, terminating EGFR activation and downstream signaling and increasing bacterial viability. Chemical inhibition and knockdown of SHP-2 expression rescued hBD3 synthesis and bactericidal activity. Thus, we reveal how cagPAI-positive H. pylori strains use CagA to evade a key innate mucosal defense pathway to support the establishment of persistent infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / metabolism*
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Down-Regulation
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism*
  • Gene Expression*
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Immune Evasion
  • Microbial Viability
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
  • Signal Transduction
  • Virulence
  • beta-Defensins / antagonists & inhibitors*
  • beta-Defensins / biosynthesis*


  • Antigens, Bacterial
  • Bacterial Proteins
  • DEFB103A protein, human
  • beta-Defensins
  • cagA protein, Helicobacter pylori
  • EGFR protein, human
  • ErbB Receptors
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11