title: Identifying Yersinia YopH-targeted signal transduction pathways that impair neutrophil responses during in vivo murine infection.
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.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA.
authors.forename: Hortensia G
authors.initials: HG
authors.lastname: Rolán
authors.forename: Enrique A
authors.initials: EA
authors.lastname: Durand
authors.forename: Joan
authors.initials: J
authors.lastname: Mecsas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction; D037521:Virulence Factors / Q000378:metabolism; D015009:Yersinia Infections / Q000276:immunology* / Q000382:microbiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001425:Bacterial Outer Membrane Proteins; D037521:Virulence Factors; D016753:Interleukin-10; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia; D002118:Calcium
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