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.

Abstract

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*

Substances

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