Modulation and dendritic cell differentiation and fuction by YopJ of Yersinia pestis

Inna Lindner, Julie Torrvellas-Garcia, Despina Kolonias, Louise M. Carlson, Khaled A. Tolba, Gregory V. Plano, Kevin P. Lee

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Yersinia pestis evades immune responses in part by injecting into host immune cells several effector proteins called Yersinia outer proteins (Yops) that impair cellular function. This has been best characterized in the innate effector cells, but much less so for cells involved in adaptive immune responses. Dendritic cells (DC) sit at the crossroads between innate and adaptive immunity, and can function to initiate or inhibit adaptive immune responses. Although Y pestis can target and inactivate DC, the mechanism responsible for this remains unclear. We have found that injection of Y pestis YopJ into DC progenitors disrupts key signal transduction pathways and interferes with DC differentiation and subsequent function. YopJ injection prevents upregulation of the NF-κB transcription factor Rel B and inhibits MAPK/ERK activation - both having key roles in DC differentiation. Furthermore, YopJ injection prevents costimulatory ligand up-regulation, LPS-induced cytokine expression, and yields differentiated DC with diminished capability to induce T cell proliferation and IFN-γ induction. By modulating DC function through YopJ-mediated disruption of signaling pathways during progenitor to DC differentiation, Yersinia may interfere with the adaptive responses necessary to clear the infection as well as establish a tolerant immune environment that leads to chronic infection/carrier state in the surviving host.

Original languageEnglish (US)
Pages (from-to)2450-2462
Number of pages13
JournalEuropean Journal of Immunology
Volume37
Issue number9
DOIs
StatePublished - Sep 2007
Externally publishedYes

Keywords

  • Dendritic cell
  • K562
  • Monocytes
  • Yersinia pestis
  • YopJ

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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