Identifying Yersinia YopH-targeted signal transduction pathways that impair neutrophil responses during in vivo murine infection

Cell Host Microbe. 2013 Sep 11;14(3):306-17. doi: 10.1016/j.chom.2013.08.013.


Identifying molecular targets of Yersinia virulence effectors, or Yops, during animal infection is challenging because few cells are targeted by Yops in an infected organ, and isolating these sparse effector-containing cells is difficult. YopH, a tyrosine phosphatase, is essential for full virulence of Yersinia. Investigating the YopH-targeted signal transduction pathway(s) in neutrophils during infection of a murine host, we find that several host proteins, including the essential signaling adaptor SLP-76, are dephosphorylated in the presence of YopH in neutrophils isolated from infected tissues. YopH inactivated PRAM-1/SKAP-HOM and the SLP-76/Vav/PLCγ2 signal transduction axes, leading to an inhibition of calcium response in isolated neutrophils. Consistent with a failure to mount a calcium response, IL-10 production was reduced in neutrophils containing YopH from infected tissues. Finally, a yopH mutant survived better in the absence of neutrophils, indicating that neutrophil inactivation by YopH by targeting PRAM-1/SKAP-HOM and SLP-76/Vav/PLCγ2 signaling hubs may be critical for Yersinia survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors*
  • Animals
  • Bacterial Outer Membrane Proteins / metabolism*
  • Calcium / metabolism
  • Host-Pathogen Interactions*
  • Immune Evasion
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / metabolism
  • Mice
  • Microbial Viability
  • Neutrophils / immunology*
  • Neutrophils / microbiology*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Tyrosine Phosphatases / metabolism*
  • Signal Transduction
  • Virulence Factors / metabolism
  • Yersinia Infections / immunology*
  • Yersinia Infections / microbiology*


  • Adaptor Proteins, Signal Transducing
  • Bacterial Outer Membrane Proteins
  • Virulence Factors
  • Interleukin-10
  • Protein Tyrosine Phosphatases
  • yopH protein, Yersinia
  • Calcium